血浆内脏脂泌素水平与冠心病相关性研究
|
摘要
背景：
随着对动脉粥样硬化发病机制的深入研究,炎症机制越来越引起重视。内脏脂泌素(visfatin)是最近发现的一种主要有内脏脂肪细胞分泌的的细胞因子,与糖尿病、肥胖、胰岛素抗体、和心血管疾病关系密切。最新的研究结果表明内脏脂泌素被证明是一种新的炎症介质,可能参与冠心病的发生发展,并在斑块不稳定状态中起重要作用。本研究对冠心病患者血浆内脏脂泌素水平进行检测,旨在探讨内脏脂泌素与冠心病的关系。
目的：
本研究主要观察血浆内脏脂泌素水平在不同类型冠心病患者血浆的变化,并与胰岛素抵抗指数(IRI),肿瘤坏死因子α(TNF-α)及血脂相比较,以探讨其与冠心病的关系。
方法：
选取郑州大学第一附属医院心内科2008年11月至2009年4月住院患者88例。经冠状动脉造影检查确诊为冠心病患者73例,其中稳定性心绞痛(SAP)30例,男18例,女12例,年龄40-79岁,平均(60.4±9.0)岁,不稳定心绞痛(UAP)23例,男14例,女9例,年龄40-75岁,平均(60.4±9.5)岁,急性心肌梗死(AMI)20例,男11例,女9例,年龄45-75岁,平均(60.4±7.3)岁,对照组15例,均为同期住院经冠脉造影后排除冠心病患者,男8例,女7例,年龄46-74岁,平均(58.1±7.4)岁。入院次晨空腹(AMI者在发病48小时以内)采静脉血,常规检测空腹血糖(FPG)及甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C),同时留血浆-80℃保存,待测空腹血浆visfatin、胰岛素及TNF-α。
结果：
①与正常对照组(15.91±4.23)ng/L相比,visfatin水平在稳定型心绞痛组(36.68±7.42)ng/L,不稳定心绞痛组(53.15±8.34)ng/L,急性心肌梗死组(72.55±7.21)ng/L均升高(p均<0.05)。TNF-α在稳定型心绞痛组(17.04±3.27)ng/L,不稳定心绞痛组(53.83±8.66)ng/L,急性心肌梗死组(73.72±12.84)ng/L,均高于正常对照组(11.17±2.58)ng/L(p均<0.05)。IRI在稳定型心绞痛组(5.63±1.71),不稳定心绞痛组(9.24±2.64),急性心肌梗死组(9.10±1.56),均高于正常对照组(2.27±0.64)(p均<0.05)。②相关分析显示脂泌素与TNF-α、IRI及LDL-C成正相关,r值分别为0.842、0.732、0.351,p<0.05,与HDL-C成负相关,r值为-0.400,p<0.05。
结论：
1.血浆脂泌素、TNF-α及IRI在CHD组明显高于对照组,提示血浆脂泌素、TNF-α及IR可能参与了冠心病的发生发展。
2.血浆脂泌素、TNF-α及IRI在AMI组和UAP组高于SAP组,提示血浆脂泌素、TNF-α及IR可能与冠状动脉粥样斑块不稳定有关。
3.脂泌素与炎症标志物TNF-α相关性分析显示呈正相关,提示脂泌素可能作为炎症因子在冠心病发生发展中起作用。
4.脂泌素与IRI在冠心病患者中呈正相关,提示脂泌素与IR均可能影响冠心病发生发展。
5.脂泌素与LDL成正相关,与HDL成负相关,表明脂泌素与血脂代谢异常有关。
Background:
As atherosclerosis is continuously researched, the inflammation mechanism is paid more attention. Visfatin is a recently discovered another new fat cell factor, it was secreted from visceral fat cell. The latest research results show that visfatin may be related to diabetes, obesity, insulin antibodies,and cardiovascular disease.The research results show that visfatin was proved to be a new inflammatory mediators may be play an important role in occurrence and development of coronary heart disease and lead to plaque vulnerability. The purpose of the study is to observe the changes of plasm visfatin level in patients with coronary heart disease, to explore the relationship between visfatin and coronary heart disease.
Aim:
The aim of the study is to observe the changes of plasm visfatin level in different types of patients with coronary heart disease,and compared with the levels of tumor necrosis factor-a(TNF-a) and insulin resistance index(IRI).In order to explore the relationship between visfatin and coronary heart disease.
Methods:
A total number of 88 in-patients who received coronary angiography in our hospital,from November 2008 to April 2009,73 patients was confirmed by coronary angiography with coronary heart disease (CHD); the coronary artery is normal for the control group in coronary angiography; CHD were divided into three groups: stable angina pectoris (SAP) group (n=30), unstable angina pectoris (UAP) group (n=23), acute myocardial infarction (AMI) group (n=20). The next morning or immediately after hospitalization,fasting venous blood of patients were collected, puting into natrium citricum anticoagulant tube,3500 r/min centrifuge for 5 min in 2 h, collecting plasm 200μL put into Ep tube storing in-80℃refrigeratory. The fasting plasma visfatin,TNF-a and insulin were examined by ELISA, and related parameters lipids were measured (cardiac muscle enzyme and CTnT were measured in UAP and AMI)
Result:
①Compared with normal control, visfatin levels [(15.91±4.23) ng/L,in normal control] were elevated in patients with SAP [(36.68±7.42) ng/L], in patients with UAP [(53.15±8.34)ng/L], and in patients with AMI [(72.55±7.21)ng/L],(allp<0.05). TNF-a levels were (17.04±3.27) ng/L in SAP, (53.83±8.66) ng/L in UAP, (73.72±12.84) ng/L in AMI, higher than the normal control group (11.17±2.58) ng/L, (allp<0.05). IRI levels were (5.63±1.71) in SAP, (9.24±2.64) in UAP, (9.10±1.56) in AMI, higher than the control group (2.27±0.64), (all p<0.05. Correlated analysis demonstrated that the fasting plasma visfatin levels was positively correlated with the levels of TNF-a, IRI and low densith lipoprotein cholesterol (LDL-C),(r:0.842、0.732、0.351, respectively, all p<0.05); but it was negatively correlated with high-density lipoprotein cholesterol (HDL-C), (r:-0.400, respectively, p<0.05).
Conclusion:
1. Plasma levels of visfatin, TNF-a and IRI in CHD group was significantly higher than that in the control group.It suggested that visfatin, TNF-a and IR play an important role in the development of CHD.
2. Plasma levels of visfatin, TNF-a and IRI in AMI group and UAP group was significantly higher than that in the SAP group.It suggested that visfatin, TNF-a and IR all related with the instability of plaques.
3. Visfatin and TNF-a was positive correlated.It suggested that visfatin may be used as inflammatory factors and play a important role in the development of CHD.
4. In CHD patients, visfatin and IRI were positive correlated.It suggested that visfatin and IR may affect the development of coronary heart disease.
5. In CHD patients,visfatin and LDL-C was positive correlated,and with HDL-C was negatively correlated.It indicated that visfatin in relation to lipid metabolic abnormalities.
随着对动脉粥样硬化发病机制的深入研究,炎症机制越来越引起重视。内脏脂泌素(visfatin)是最近发现的一种主要有内脏脂肪细胞分泌的的细胞因子,与糖尿病、肥胖、胰岛素抗体、和心血管疾病关系密切。最新的研究结果表明内脏脂泌素被证明是一种新的炎症介质,可能参与冠心病的发生发展,并在斑块不稳定状态中起重要作用。本研究对冠心病患者血浆内脏脂泌素水平进行检测,旨在探讨内脏脂泌素与冠心病的关系。
目的：
本研究主要观察血浆内脏脂泌素水平在不同类型冠心病患者血浆的变化,并与胰岛素抵抗指数(IRI),肿瘤坏死因子α(TNF-α)及血脂相比较,以探讨其与冠心病的关系。
方法：
选取郑州大学第一附属医院心内科2008年11月至2009年4月住院患者88例。经冠状动脉造影检查确诊为冠心病患者73例,其中稳定性心绞痛(SAP)30例,男18例,女12例,年龄40-79岁,平均(60.4±9.0)岁,不稳定心绞痛(UAP)23例,男14例,女9例,年龄40-75岁,平均(60.4±9.5)岁,急性心肌梗死(AMI)20例,男11例,女9例,年龄45-75岁,平均(60.4±7.3)岁,对照组15例,均为同期住院经冠脉造影后排除冠心病患者,男8例,女7例,年龄46-74岁,平均(58.1±7.4)岁。入院次晨空腹(AMI者在发病48小时以内)采静脉血,常规检测空腹血糖(FPG)及甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C),同时留血浆-80℃保存,待测空腹血浆visfatin、胰岛素及TNF-α。
结果：
①与正常对照组(15.91±4.23)ng/L相比,visfatin水平在稳定型心绞痛组(36.68±7.42)ng/L,不稳定心绞痛组(53.15±8.34)ng/L,急性心肌梗死组(72.55±7.21)ng/L均升高(p均<0.05)。TNF-α在稳定型心绞痛组(17.04±3.27)ng/L,不稳定心绞痛组(53.83±8.66)ng/L,急性心肌梗死组(73.72±12.84)ng/L,均高于正常对照组(11.17±2.58)ng/L(p均<0.05)。IRI在稳定型心绞痛组(5.63±1.71),不稳定心绞痛组(9.24±2.64),急性心肌梗死组(9.10±1.56),均高于正常对照组(2.27±0.64)(p均<0.05)。②相关分析显示脂泌素与TNF-α、IRI及LDL-C成正相关,r值分别为0.842、0.732、0.351,p<0.05,与HDL-C成负相关,r值为-0.400,p<0.05。
结论：
1.血浆脂泌素、TNF-α及IRI在CHD组明显高于对照组,提示血浆脂泌素、TNF-α及IR可能参与了冠心病的发生发展。
2.血浆脂泌素、TNF-α及IRI在AMI组和UAP组高于SAP组,提示血浆脂泌素、TNF-α及IR可能与冠状动脉粥样斑块不稳定有关。
3.脂泌素与炎症标志物TNF-α相关性分析显示呈正相关,提示脂泌素可能作为炎症因子在冠心病发生发展中起作用。
4.脂泌素与IRI在冠心病患者中呈正相关,提示脂泌素与IR均可能影响冠心病发生发展。
5.脂泌素与LDL成正相关,与HDL成负相关,表明脂泌素与血脂代谢异常有关。
Background:
As atherosclerosis is continuously researched, the inflammation mechanism is paid more attention. Visfatin is a recently discovered another new fat cell factor, it was secreted from visceral fat cell. The latest research results show that visfatin may be related to diabetes, obesity, insulin antibodies,and cardiovascular disease.The research results show that visfatin was proved to be a new inflammatory mediators may be play an important role in occurrence and development of coronary heart disease and lead to plaque vulnerability. The purpose of the study is to observe the changes of plasm visfatin level in patients with coronary heart disease, to explore the relationship between visfatin and coronary heart disease.
Aim:
The aim of the study is to observe the changes of plasm visfatin level in different types of patients with coronary heart disease,and compared with the levels of tumor necrosis factor-a(TNF-a) and insulin resistance index(IRI).In order to explore the relationship between visfatin and coronary heart disease.
Methods:
A total number of 88 in-patients who received coronary angiography in our hospital,from November 2008 to April 2009,73 patients was confirmed by coronary angiography with coronary heart disease (CHD); the coronary artery is normal for the control group in coronary angiography; CHD were divided into three groups: stable angina pectoris (SAP) group (n=30), unstable angina pectoris (UAP) group (n=23), acute myocardial infarction (AMI) group (n=20). The next morning or immediately after hospitalization,fasting venous blood of patients were collected, puting into natrium citricum anticoagulant tube,3500 r/min centrifuge for 5 min in 2 h, collecting plasm 200μL put into Ep tube storing in-80℃refrigeratory. The fasting plasma visfatin,TNF-a and insulin were examined by ELISA, and related parameters lipids were measured (cardiac muscle enzyme and CTnT were measured in UAP and AMI)
Result:
①Compared with normal control, visfatin levels [(15.91±4.23) ng/L,in normal control] were elevated in patients with SAP [(36.68±7.42) ng/L], in patients with UAP [(53.15±8.34)ng/L], and in patients with AMI [(72.55±7.21)ng/L],(allp<0.05). TNF-a levels were (17.04±3.27) ng/L in SAP, (53.83±8.66) ng/L in UAP, (73.72±12.84) ng/L in AMI, higher than the normal control group (11.17±2.58) ng/L, (allp<0.05). IRI levels were (5.63±1.71) in SAP, (9.24±2.64) in UAP, (9.10±1.56) in AMI, higher than the control group (2.27±0.64), (all p<0.05. Correlated analysis demonstrated that the fasting plasma visfatin levels was positively correlated with the levels of TNF-a, IRI and low densith lipoprotein cholesterol (LDL-C),(r:0.842、0.732、0.351, respectively, all p<0.05); but it was negatively correlated with high-density lipoprotein cholesterol (HDL-C), (r:-0.400, respectively, p<0.05).
Conclusion:
1. Plasma levels of visfatin, TNF-a and IRI in CHD group was significantly higher than that in the control group.It suggested that visfatin, TNF-a and IR play an important role in the development of CHD.
2. Plasma levels of visfatin, TNF-a and IRI in AMI group and UAP group was significantly higher than that in the SAP group.It suggested that visfatin, TNF-a and IR all related with the instability of plaques.
3. Visfatin and TNF-a was positive correlated.It suggested that visfatin may be used as inflammatory factors and play a important role in the development of CHD.
4. In CHD patients, visfatin and IRI were positive correlated.It suggested that visfatin and IR may affect the development of coronary heart disease.
5. In CHD patients,visfatin and LDL-C was positive correlated,and with HDL-C was negatively correlated.It indicated that visfatin in relation to lipid metabolic abnormalities.
引文
[1]Trayhurn P, Wood IS, Adipokines:inflammation and the pleiotropic role of white adipose tissue. Br J Nutr.2004 Sep; 92(3):347-55.
[2]Fukuhara A, Matsuda M:2005. Visfatin:a protein secreted by visceral fat that mimics the effects of insulin. Science 307:426-430.
[3]Hammarstedt A, Pihlajamaki J, Rotter SopasakisV, et al. Visfatin is an adi pokine but it is not regulated by thiazolidinedi ones. J Clin EndocrinolMetab,2006,91:1181-1184
[4]Koh EH, Kim MS, Park JY, et al. Peroxisome proliferator-activated receptor (PPAR)-alpha activation prevents diabetes in OLETF rats:comparison with PPAR-gamma activation. Diabetes.2003 Sep; 52(9):2331-7.
[5]潘晓仁,杨文英,刘娟,等.1994年中国糖尿病患病率及危险因素.中华内科杂志,1997；6：384-9
[6]Frydelund2 Larsen L, Akerstrom T, Nielsen S, et al. Visfatin mRNA express on in human subcutaneous adipose tissue is regulated by exercise [J]. Am J Physiol EndocrinolMetab, 2007,292(1):E242-31.
[7]Fasshauer M, Klein J, Lossner U, Paschke R. Interleukin (IL)-6 mRNA expression is stimulated by insulin, isoproterenol, tumour necrosis factor alpha, growth hormone, and IL-6 in 3T3-L1 adipocytes. Horm Metab Res.2003 Mar; 35(3):147-52.
[8]Ye SQ, Zhang LQ, Adyshev D, Usatyuk PV, Garcia AN, et al. Pre-B-cell-colony-enhancing factor is critically involved in thrombin-induced lung endothelial cell barrier dysregulation. Microvasc Res.2005 Nov; 70 (3):142-51. Epub 2005 Sep 26.
[9]McPherson R, Jones PH. The metabolic syndrome and type 2 diabetes:role of the adipocyte. Curr Opin Lipidol.2003 Dec; 14 (6):549-53.
[10]Kralisch S, Klein J, Lossner U, et al. Hormonal regulation of the novel adipocytokine visfatin in 3T3-L1 adipocytes. J Endocrinol.2005 Jun; 185 (3):R1-8.
[11]Damore MA, Omori SA, Wall R. IFN-gamma induces the kappa intron enhancer via an IFN-stimulated response element. J Immunol.1996 Apr 1; 156 (7):2451-7.
[12]Wajchenberg BL, Giannella-Neto D, Da Silva ME, Santos RF. Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome. Horm Metab Res.2002 Nov-Dec; 34 (11-12):616-21.
[13]Cohen J. Scientific publication. HHS Asks PNAS to pull bioterr-orism paper. Science. 2005 Jun 3; 308 (5727):1395.
[14]Li H, Liu P, Cepeda J, et al. Augmentation of Pulmonary Epithelial Cell IL-8 Expression and Permeability by Pre-B-cell Colony Enhancing Factor. J Inflamm (Lond).2008 Sep 22; 5-15.
[15]Haider DG, Pleiner J, Francesconi M, et al:2006. Exercise training lowers plasma visfatin concentrations in patients with type 1 diabetes. J Clin Endocrinol Metab 91:4702-4704.
[16]Bottcher Y, Teupser D, Enigk B, Berndt J, Kloting N, et al; Genetic variation in the visfatin gene (PBEF1) and its relation to glucose metabolism and fat-depot-specific messenger ribonucleic acid expression in humans. J Clin Endocrinol Metab.2006 Jul;91 (7):2725-31. Epub 2006 Apr 24.
[17]Sethi JK, Vidal-Puig A. et al:Visfatin:the missing link between intra-abdominal obesity and diabetes? Trends Mol Med.2005 Aug; 11 (8):344-7.
[18]Van der Veer E, Nong Z, O'Neil C, et al. Pre-B-cell colony-enh-ancing factor regulates NAD+-dependent protein deaetylase activity and promotes vascular smooth muscle cell maturation. Circ Res 2005; 1:25-34.
[19]Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I. Cloning and characterization of the cDNA encoding a novel human pre-B cell colony-enhancing factor. Mol Cell Biol 1994; 14:1431-7.
[20]Jia SH, Li Y, Parodo J, Kapus A, Fan L, Rotstein OD, et al. Pre-Bcell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis. J Clin Invest 2004; 113:1318-27.
[21]Guerci B, Bohme P, Kearney-Schwartz A, Zannad F, Drouin P.:Diabetes Metab. Endothelial dysfunction and type 2 diabetes. Part 2:altered endothelial function and the effects of treatments in type 2 diabetes mellitus.2001 Sep; 27 (41):436-47.
[22]Lopez-Bermejo A, Chico-Julia B, Fernandez-Balsells M, Recasens M, Esteve E, Casamitjana R, et al. Serum visfatin increases with progressive beta-cell deterioration. Diabetes 2006;55:2871-5
[23]Dahl TB, Yndestad A, Skjelland M, Oie E, Michelsen A, Damas JK, et al. Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis:possible role in inflammation and plaque destabilization. Circulation 2007; 115:972-80.
[24]Moschen AR, Kaser A, Enrich B, et al:2007.Visfatin, an adipocyto -kine with proinflammatory and immunomodulating properties. J Immunol 178:1748-1758.
[25]Liu SW, Qiao SB, et al. Association of plasma visfatin levels with inflammation, atherosclerosis and acute coronary syndromes (ACS) in humans.[J].Clin Endocrinol (Oxf). 2009,71(2):202-7.
[26]Harper N, Hughes M, MacFarlane M, Cohen GM. Fas-associated death domain protein and caspase-8 are not recruited to the tumor necrosis factor receptor 1 signaling complex during tumor necrosis factor-induced apoptosis.J Biol Chem.2003 Jul 11; 278(28):25534-41. Epub 2003 Apr 29.
[27]Bazanova EA, Bukhova VP, Liampert IM. The role of non-type-specific protein antigens of the cell wall in Streptococcus group A in developing delayed hypersensitivity.Zh Mikrobiol Epidemiol Immunobiol.1987 Aug; (8):67-71.
[28]Baxter, G. T, Kuo, R. C, Jupp, O J, Vandenabeele, P.,& MacEwan, D. J (1999). Tumor necrosis factora mediates both apoptotic cell death and cell proliferation in a human hematopoietic cell line dependent on mitotic activity and receptor subtype expression. J Biol Chem274; 9539-9547.
[29]Li XQ, Zhao MG, Mei QB, Zhang YF, Guo W, Wang HF, Chen D, Cui Y. Effects of tumor necrosis factor-alpha on calcium movement in rat ventricular myocytes. Acta Pharmacol Sin.2003 Dec;24(12):1224-30.
[30]Harper N, Hughes M, MacFarlane M, Cohen GM. Fas-associated death domain protein and caspase-8 are not recruited to the tumor necrosis factor receptor 1 signaling complex during tumor necrosis factor-induced apoptosis.J Biol Chem.2003 Jul 11; 278(28):25534-41. Epub 2003 Apr 29.
[31]Beletsky IP, Moshnikova AB, Proussakova OV. Cytotoxic signal transduction pathways via TNF family receptors. Biochemistry (Mosc).2002 Mar; 67 (3):312-28.
[32]Sack, M. N., Smith, R. M.,& Opie, L. H. (2000). Tumor necrosis factor in myocardial hypertrophy and ischaemiaan anti-apoptotic perspective. Cardiovasc Res 45,688-695.
[33]Wang M, Tsai BM, Crisostomo PR, Meldrum DR. Tumor necrosis factor receptor 1 signaling resistance in the female myocardium during ischemia.Circulation.2006 Jul 4; 114: 282-9.
[34]Yasukawa H, Hoshijima M, Gu Y, Nakamura T, Pradervand S, et al:Suppressor of cytokine signaling-3 is a biomechanical stress -inducible gene that suppresses gp130-mediated cardiac myocyte hypertrophy and survival pathways. J Clin Invest.2001 Nov;108 (10):1459-67.
[35]Baines, C. P, Cohen, M. V,& Downey, J. M. (1999). Signal transduction in ischemic preconditioning:the role of kinases and Mitochondrial K(ATP) channels. J Cardiovasc Electrophysiol 10,741-754.
[36]Zechner, D., Craig, R., Hanford, D. S., McDonough, P. M., Sabbadini, R. A,& Glembotski, C. C. (1998). MKK6 activates myocardial cell NF-kappaB and inhibits apoptosis in a p38 mitogen-activated protein kinase-dependent manner. J Biol Chem 273,8232-8239.
[37]Lazou A, Sugden PH, Clerk A. Activation of mitogen-activated protein kinases (p38-MAPKs, SAPKs/JNKs and ERKs) by the G-protein-coupled receptor agonist phenylephrine in the perfused rat heart. Biochem J.1998 Jun 1; 332 (2):459-65.
[38]Haudek, S. B., Bryant, D. D.,& Giroir, B. P. (2001). Differential regulation of myocardial NF kappa B following acute or chronic TNF-alpha exposure. J Mol Cell Cardiol 33,1263-1271.
[39]Haunstetter, A.,& Izumo, S. (1998). Apoptosisbasic mechanisms and implications in cardiovascular disease. Circ Res 82,1111-1129.
[40]Wallach, D. (1997). Cell death induction by TNF:a matter of self control.Trends Biochem Sci 22,107-109.
[41]Bowden RA, Ding ZM, Donnachie EM, Petersen TK, Michael LH, Ballantyne CM, Burns AR. Role of alpha4 integrin and VCAM-1 in CD 18-independent neutrophil migration across mouse cardiac endothelium. Circ Res.2002 Mar 22; 90(5):562-9..
[42]Barath, P., Fishbein, M. C., Cao, J., Berenson, J., Helfant, R. H.,& Forrester, J. S. (1990). Detection and localization of tumor necrosis factor in human atheroma. Am J Cardiol 65, 297-302.
[43]Napoli, C., Quehenberger, O., De Nigris, F., Abete, P., Glass, C. K.,& Palinski, W. (2000). Mildly oxidized low density lipoprotein activates multiple apoptotic signaling pathways in human coronary cells. FASEB J14,1996-2007.
[44]Niemann-Jonsson, A., Dimayuga, P., Jovinge, S., Calara, F., Ares, M. P., Fredrikson, G. N., &Nilsson, J. (2000). Accumulation of LDL in ratarteries is associated with activation of tumor necrosis factor alpha expression. Arterioscler Thromb Vasc Biol 20,2205-2211.
[45]Binion DG, Rafiee P. Is inflammatory bowel disease a vascular disease? Targeting angiogenesis improves chronic inflammation in inflammatory bowel disease. Gastroenterology.2009 Feb; 136 (2):400-3. Epub 2008 Dec 26.
[46]Schonbeck U, Mach F, Sukhova GK, Murphy C, Bonnefoy JY, Fabunmi RP, Libby P. Regulation of matrix metalloproteinase expression in human vascular smooth muscle cells by T lymphocytes:a role for CD40 signaling in plaque rupture? Circ Res.1997 Sep; 81(3):448-54.
[47]Geng, Y. J., Wu, Q., Muszynski, M., Hansson, G K.,& Libby, P. (1996). Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta. Arterioscler Thromb Vasc Biol 16,19-27.
[48]Okura Y, Brink M, Itabe H, Scheidegger KJ, Kalangos A, Delafon -taine P. Oxidized low-density lipoprotein is associated with apoptosis of vascular smooth muscle cells in human atherosclerotic plaques Circulation.2000 Nov 28; 102(22):2680-6.
[49]Ferro, D., Parrotto, S., Basili, S., Alessandri, C.,& Violi, F. (2000) Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia. J Am Coll Cardiol 36427-431.
[50]Ridker, P. M., Rifai, N., Pfeffer, M. A., Sacks, F.,& Braunwald, E. (1999).Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation 100,230-235.
[51]Simes RJ, Marschner IC, Hunt D, Colquhoun D, Sullivan D, et al:Relationship between lipid levels and clinical outcomes in the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Trial:to what extent is the reduction in coronary events with pravastatin explained by on-study lipid levels?. Circulation.2002 Mar 12; 105(10):1162-9.
[52]Schieffer B, Biinte C, Witte J, Hoeper K, Boger RH, Schwedhelm E, Drexler H. Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease. J Am Coll Cardiol.2004 Jul 21; 44(2):362-8.
[53]Lee SK, Kim CS, Yang WS, Kim SB, Park SK, Park JS. Exogenous nitric oxide inhibits tumor necrosis factor-alpha or interleukin-1 beta-induced monocyte chemoattractant protein-1 expression in human mesangial cells. Role of IkappaB-alpha and cyclic GMP. Nephron.2002 Dec; 92(4):780-7.
[54]Kuzuya T, Nakagawa S, Satoh J, Kanazawa Y, Iwamoto Y, et al. Report of the Committee on the classification and diagnostic criteria of diabetes mellitus. Diabetes Res Clin Pract. 2002 Jan; 55(1):65-85.
[55]Patrik L,Vaessa Van H,Signy R,et al.Secretion of TNF-a shows a strong relationship to insulinstimulated gluose transport in human adipose tissue.Diabetes,2000; 49(5):688.
[56]Sarzi-Puttini P, Atzeni F, Shoenfeld Y, Ferraccioli G. TNF-alpha, rheumatoid arthritis, and heart failure:a rheumatological dilemma. Autoimmun Rev.2005 Mar; 4(3):153-61.
[57]Banfi C, Mussoni L, Tremoli E. PAI-1, the primary plasmatic inhibitor of fibrinolysis. Physiopathologic role and molecular mechan -isms. Minerva Endocrinol.2002 Sep; 27(3): 181-91.
[58]Aljada A,Ghanim H,Assian E,et al.TNF-α in hibits insulin induled increase in endothelial nitric oxide synthase and reduces insulinr-eceptor conteanphosphorylation.Metabolism, 2002;51(4):487.
[59]Sartippour MR, Renier G. Differential regulation of macrophage peroxisome proliferator-activated receptor expression by glucose:role of peroxisome proliferator-activated receptors in lipoprotein lipase gene expression. Arterioscler Thromb Vasc Biol.2000 Jan; 20(1):104-10.
[60]Mishima Y, Kuyama A, Tada A, Relationship between TNF-a and insulin resistance in obese men with T2DM.Diabetes Research Clinical Practice,2001;52 (2); 119.
[61]闫胜利,胰岛素抵抗与脂代谢异常。山东医药2003；43(13)：
[62]陈蕾,贾伟平,项坤三,葡萄糖嵌夹技术在糖尿病研究中的应用.中华内分泌代谢杂志,2003；19(1)：74-6.
[63]Mnttllews DR, HoskerJP, RudeI18kiAs, et al Homeostasis model assessment:insulin resistance and beta cell function from fasting plasma glucose and lnslllin concentration in man [J].Diabetoto-gia,1985,28(11):412-419
[64]Giovanni P, Pao10 G, Adriaan A, et al.Cardiac and skeletal muscle insulin resistance in patients with coronary heart disease [J]. Clin. invest.1996,98(11):2094-2099.
[65]Hrnciar J.. Amylin as an additional possible pathogenic factor in NIDDM and the insulin resistance syndrome [J]. Vnitr Lek.1996 Aug;42 (8):557-60.
[66]Hanley AJ, Williams K, Stern MP et al. Homeostasis modelasses -smentof insulin resistance in relation to the incidence of cardio-vascular disease:the San Antonio Heart Study. Diabetes Care 2002; 25(7):1177-1184.
[67]Pirro M, Mauriege P, Tchern of A, Cantin B. et al. Plasma free fatty acid levels and the risk of ischemic heart disease in men:prospective results from the Quebec Cardiovascular Study.Atherosclerosis.2002 Feb; 160(2):377-84.
[68]Pyorala K, Savolainen E, Kaukola S et al. Plasma insulin as coronary heart disease risk factor:relationship to other risk factors and predictive value during 91/2-year follow-up of the Helsinki Policemen Study population. Acta Medica Scandinavica. Supplemen-turn 1985; 701:38-52.
[69]Ducimetiere P, Eschwege E, Papoz L et al. Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population. Diabetologia 1980; 19(3):205-210.
[70]Nystrom T. The potential beneficial role of glucagon-like peptide-1 in endothelial dysfunction and heart failure associated with insulin resistance. Horm Metab Res.2008 Sep; 40(9):593-606. Epub 2008 Sep 15.
[71]Arnal JF, Dinh-Xuan AT, Pueyo M, Darblade B, Rami J.Endothelium-derived nitric oxide and vascular physiology and pathology. Cell Mol Life Sci.1999 Jul; 55(8-9):1078-87.
[72]Potenza MA, Marasciulo FL, Chieppa DM et al. Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production. American Journal of Physiology. Heart and Circulatory Physiology 2005; 289(2):H813-H822.
[73]Peppa M, Vlassara H. Advanced glycation end products and diabetic complications:a general overview. Hormones (Athens).2005 Jan-Mar; 4(1):28-37.
[74]Iozzo P, Chareonthaitawee P, Rimoldi O, et al. Mismatch between insulin-mediated glucose uptake and blood flow in the heart of patients with Type Ⅱ diabetes. Diabetologia.2002 Oct; 45(10):1404-9. Epub 2002 Jul 27.
[75]Natali A, Buzzigoli G, Taddei S, Santoro D, Cerri M, Pedrinelli R, Ferrannini E. Effects of insulin on hemodynamics and metabolism in human forearm. Diabetes.1990 Apr; 39(4):490-500.
[76]Sondergaard HM, Bottcher M, Marie Madsen M, et al. Impact of type 2 diabetes on myocardial insulin sensitivity to glucose uptake and perfusion in patients with coronary artery disease. J Clin Endocrinol Metab.2006 Dec; 91(12):4854-61. Epub 2006 Sep 19.
[77]Paternostro G, Camici PG, Lammerstma AA, et al. Cardiac and skeletal muscle insulin resistance in patients with coronary heart disease. A study with positron emission tomography. J Clin Invest 1996;98(November (9)):2094-9.
[78]Pagano C, Pilon C, Olivieri M, Mason P, Fabris R, et al. Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to insulin resistance in humans.. J Clin Endocrinol Metab.2006 Aug; 91(8):3165-70. Epub 2006 May 23.
[79]Krzyzanowska K, Krugluger W, Mittermayer F, Rahman R, Haider D, Shnawa N, Schernthaner G. Increased visfatin concentrations in women with gestational diabetes mellitus. Clin Sci (Lond).2006 May; 110(5):605-9.
[80]Lamarche B, Tchernof A, Mauriege P, Cantin B, Dagenais GR, Lupien PJ, Despres JP. Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease. JAMA.1998 Jun 24; 279(24):1955-61.
[1]Fantuzzi G., Adipose tissue, adipokines, and inflammation[J].J Aller-gy Clin.Immunol, 2005,115:911-919.
[2]Fukuhara A, Matsuda M, Nishizawa M, et al. Visfatin:a protein secreted by visceral fat that mimics the effects of insulin [J]. Science,2005,307:426-430.
[3]Sethi JK, Vidal2 Puig A. Visfatin:the missing link between intra-abdominal obesity and diabetes? Trends Mol Med,2005,11:344-347.
[4]J ia S H, Li Y, Par odo J, et al. Pre2 B cell col ony2 enhancing factor inhibits neutrophil apoptosis in experi mental inflammati on and clinical sepsis [J]. J Clin Invest,2004,113 (9): 1318-1327.
[5]Bajwa EK, Yu CL, Gong MN, Thompson BT, Christiani DC. Pre-B-cellcolony-enhancing factor gene polymorphisms and risk of acute respiratory distress syndrome. Crit Care Med. 2007 May; 35 (5):1290-5.
[6]Berndt J, Kloting N, Kralisch S,et al. Plasma visfatin concen-trations and fat depot-specific mRNA expression in humans. Diabetes 2005; 54:2911-2916.
[7]Jia SH, Li Y, Parodo J, et al. Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis. J Clin Invest 2004; 113:1318-1327.
[8]Ognjanovic S, Bao S, Yamamoto S Y, et al. Genomic organization of the gene coding for human p re2 B2 cell colony enhancing facto and expressi on in human fetal membranes[J]. J Mol Endocrinol 2001,26 (2):1072-117.
[9]Samal B, Sun Y, Stearns G, et al. Cloning and characterizati on of the cDNA encoding a novel human p re2 B2 cell colony-enhancing factor [J]. Mol Cell Biol,1994,14 (2):14312 1437:
[10]Steppan CM, Wang J, Whiteman EL,et al.Activation of SOCS-3 by resistin.Mol Cell Biol,2005,25:1569-1575
[11]Banerjee RR, Rangwala SM, Shapiro JS, et al.Regulation of fasted blood glucose by resistin,Science,2004,303:1195-1198.
[12]Sato N, Kobayashi K, Inoguchi T, et al.Adenovinus-mediated high expression of resistin causes dyslipidemia in mice.Endocrinology,2005,146:273-279.
[13]Satoh H,Nguyen MT,Miles PD, et al.Adenovirus-mediated chronic " hyperresistinemia" leads to in vivo insulin resistance in normal rats.J Clin Invest,2004,114:224-231.
[14]Moon B,Kwan JJ,Duddy N,et al.Resistin inhibits glucose uptake in L6 cells independently of changes in insulin signaling and GLUT4 translocation.Am J Endocrinol Metab,2003,285:E106-E115.
[15]ChenMP, Chung FM,Chang D M, et al,Elevated plasma level of visfatin/Pre-B cell colony-enhancing factor in patients with type 2 diabets.J Clin Endocrinol Metab,2006,Jan, 91(1):295-299
[16]Yoshinor,Archana,Masafumi,et al.Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic pati-ents.The Journal of Clinical Endocrinology & Metabolis-m,2005,87(6):2784-2791.
[17]Choi KC, Ryu OH, Lee KW, et al. Effect of PPAR-alpha and-gamma agonist on the expression of visfatin, adiponectin, and TNF-alpha in visceral fat of OLETF rats. Biochem Biophys Res Commun 2005;
[18]Hammarstedt A, Pihlajamaki J, Rotter SopasakisV, et al. Visfatin is an adi pokine but it is not regulated by thiazolidinedi ones. J Clin EndocrinolMetab,2006,91:1181-1184
[19]Gaber T, Dziurla R, TschirschmannM, et al. The effect of hypoxia on the exp ression of pbef in CD4+Lymphocytes[J]. Ann Rheum Dis,2006,65 (6):455.
[20]Bae S K, Kim S R, Kim J G, et al. Hypoxic inducti on of human visfatin gene is directly mediated by hypoxia2inducible factor 1[J]. FEBS Lett,2006,580 (17):41052 4113.
[21]Frydelund2 Larsen L, Akerstrom T, Nielsen S, et al. Visfatin mRNA exp ressi on in human subcutaneous adi pose tissue is regulated by exercise [J]. Am J Physiol EndocrinolMetab, 2007,292(1):E242-31.
[22]Kralisch S, Klein J, Lossner U, et al. Isoproterenol, TNFalpha, and insulin downregulate adipose triglyceride lipase in 3T3-L1 adipocytes. Mol Cell Endocrinol 2005; 240:43-49.
[23]Arner P. Visfatin2 A true or false trail t o type 2 diabetes mellitus [J]. J Clin EndocrinolMetab,2006,91 (1):28230.
[24]Kralisch S, Klein J, Lossner U, et al. Interleukin-6 is a negative regulator of visfatin gene expression in 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab 2005; 289:E586-E590.
[25]Patr one L, DamoreaM A, LeeM B, et al. Genes exp ressed during the IFNy-induced maturation of pre-B cells [J]. Mol I mmunol,2001,38 (8):5972 606.
[26]Haider DG, Plenier J, Francesconi M,et al.Exercise training lowers plasma visfatin concentrations in patients with type 1 diabetes [J].J Clin Endocrinol Metab,2006,91(11): 4702-4704.
[27]Steppan CM,Bailey ST,Bhat S,et al.The hormone resistin links obesity to diabetes. Nature, 2001,409:307-312.
[28]ChenMP, Chung FM, Chang DM, et al. Elevated plasma level of visfatin/Pre-B cell col-onyenhancing fact or in pa-tients with type 2 diabetes mellitus. J Clin Endocrinol Metab, 2006,91:295-299.
[29]Lopez-Bermejo A,Chico-Julia B,Fernandez-Balsells M,et al.Serum visfatin increase with progressive{beta}-cell deterioration [J].Diabetes,2006,55(10):2871-2875
[30]Dogru T,Sonmez A, Tasci I, et al.Plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabets mellitus and impaired glucose tolerance[J]. Diabetes Res Clin Pract,2007,76 (1):24-29
[31]Krzyzanowska K, Krugluger W, Mittermayer F, et al.Increased visfatin concentrations in women with gestational diabetes mellitus[J]. Clin Sci (Lond),2006,110 (5):605-609.
[32]Kitani T, Okuno S, Fujisawa H. Growth phase-dependent changes in the subcellular localization of pre-B cell colony-enhancing factor. FEBS Lett 2003; 544:74-78.
[33]Cinti S, Mitchell G, Barbatelli G, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46:2347-2355.
[34]Haider DG, Schindler K, Schaller G, et al. Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding [J].J Clin Endocrinol Metab, 2006,91(4):1578-1581.
[35]Pagano C,Pilon C,Olivieri M,et al. Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to insulin resistance in humans [J].J Clin Endocrinol Metab,2006,91 (8):3165-3170
[36]Kloting N, Kloting I. Visfatin:gene expression in isolated adipocytes and sequence analysis in obese WOKW rats compared with lean control rats. Biochem Biophys Res Commun 2005; 332:1070-1072.
[37]Samal B, Sun Y, Stearns G, et al. Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol Cell Biol 1994; 14:1431-1437.
[38]McGlothlin JR, Gao L, Lavoie T, Simon BA, Easley RB, et al. Molecular cloning and characterization of canine pre-B-cell colony-enhancing factor. Biochem Genet.2005 Apr; 43(3-4):127-41.
[39]Van der Veer E, Nong Z, O'Neil C, et al. Pre-B-cell colony-enhancing factor regulates NAD+dependent protein deacetylase activity and promotes vascular smooth muscle cell maturation. Circ Res 2005; 1:25-34.
[40]Haider DG, Schindler K,Schaller G, cr al. Increased plasma level visfatin concentrations in morbidly obese subjects are reduced after gastric banding[J].J Clin Endocrinol Metab, 2005,91:3165-3170.
[41]Schindler K,Haider D,Wolzt M,et al.Impact of anti-retroviral therapy on visfatin and retinol-binding protein 4 in HIV-infected subjects[J].Eur J Clin Invest,2006,36(9):640-646.
[42]Bemdt J, Kloting N, Kralisch S, et at.Plasma visfatin concentrat-ions and fat depet-specific mRNA expresson in humans [J]. Diabetes,2005,54(10):2911-2916.
[43]Moschen AR,Kaser A,Enrich B,et al. Visfatin,an adipocytokine with proinflammatory and immunomodulating properties[J].J Immunol,2007,178(3):1748-1758.
[44]Dahl TB, Yndestad A, Skjelland M. Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis:possible role in inflammation and plaque destabilization [J].Circulation,2007,115(8):972-980.
[45]Liu SW, Qiao SB, et al. Association of plasma visfatin levels with inflammation, atherosclerosis and acute coronary syndromes (ACS) in humans. [J].Clin Endocrinol (Oxf). 2009,71(2):202-7.
[46]Pillai JB, Isbatan A ImaiS,et al. Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2a deacetylase activity[J].J Biol Chem,2005,280:43121-43130
[47]Ye SQ, Zhang LQ, Adyshev D, et al. Pre-B-cell-colony-enhancing factor is critically involved in thrombin-induced lung endothelial cell barrier dysregulation. Microvasc Res. 2005; Sep 23 [Epub ahead of print].
[48]Ognjanovic S, Bryant-Greenwood GD. Pre-B-cell colony-enhancing factor, a novel cytokine of human fetal membranes. Am J Obstet Gynecol 2002; 187:1051-1058.
[49]Rongvaux A, Shea RJ, Mulks MH, et al. Pre-B-cell colony-enhancing factor, whose expression is upregulated in activated lymphocytes, is a nicotinamide phosphoribosyl transferase, a cytosolic enzyme involved in NAD biosynthesis. Eur J Immunol 2002; 11:3225-3234.
[2]Fukuhara A, Matsuda M:2005. Visfatin:a protein secreted by visceral fat that mimics the effects of insulin. Science 307:426-430.
[3]Hammarstedt A, Pihlajamaki J, Rotter SopasakisV, et al. Visfatin is an adi pokine but it is not regulated by thiazolidinedi ones. J Clin EndocrinolMetab,2006,91:1181-1184
[4]Koh EH, Kim MS, Park JY, et al. Peroxisome proliferator-activated receptor (PPAR)-alpha activation prevents diabetes in OLETF rats:comparison with PPAR-gamma activation. Diabetes.2003 Sep; 52(9):2331-7.
[5]潘晓仁,杨文英,刘娟,等.1994年中国糖尿病患病率及危险因素.中华内科杂志,1997；6：384-9
[6]Frydelund2 Larsen L, Akerstrom T, Nielsen S, et al. Visfatin mRNA express on in human subcutaneous adipose tissue is regulated by exercise [J]. Am J Physiol EndocrinolMetab, 2007,292(1):E242-31.
[7]Fasshauer M, Klein J, Lossner U, Paschke R. Interleukin (IL)-6 mRNA expression is stimulated by insulin, isoproterenol, tumour necrosis factor alpha, growth hormone, and IL-6 in 3T3-L1 adipocytes. Horm Metab Res.2003 Mar; 35(3):147-52.
[8]Ye SQ, Zhang LQ, Adyshev D, Usatyuk PV, Garcia AN, et al. Pre-B-cell-colony-enhancing factor is critically involved in thrombin-induced lung endothelial cell barrier dysregulation. Microvasc Res.2005 Nov; 70 (3):142-51. Epub 2005 Sep 26.
[9]McPherson R, Jones PH. The metabolic syndrome and type 2 diabetes:role of the adipocyte. Curr Opin Lipidol.2003 Dec; 14 (6):549-53.
[10]Kralisch S, Klein J, Lossner U, et al. Hormonal regulation of the novel adipocytokine visfatin in 3T3-L1 adipocytes. J Endocrinol.2005 Jun; 185 (3):R1-8.
[11]Damore MA, Omori SA, Wall R. IFN-gamma induces the kappa intron enhancer via an IFN-stimulated response element. J Immunol.1996 Apr 1; 156 (7):2451-7.
[12]Wajchenberg BL, Giannella-Neto D, Da Silva ME, Santos RF. Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome. Horm Metab Res.2002 Nov-Dec; 34 (11-12):616-21.
[13]Cohen J. Scientific publication. HHS Asks PNAS to pull bioterr-orism paper. Science. 2005 Jun 3; 308 (5727):1395.
[14]Li H, Liu P, Cepeda J, et al. Augmentation of Pulmonary Epithelial Cell IL-8 Expression and Permeability by Pre-B-cell Colony Enhancing Factor. J Inflamm (Lond).2008 Sep 22; 5-15.
[15]Haider DG, Pleiner J, Francesconi M, et al:2006. Exercise training lowers plasma visfatin concentrations in patients with type 1 diabetes. J Clin Endocrinol Metab 91:4702-4704.
[16]Bottcher Y, Teupser D, Enigk B, Berndt J, Kloting N, et al; Genetic variation in the visfatin gene (PBEF1) and its relation to glucose metabolism and fat-depot-specific messenger ribonucleic acid expression in humans. J Clin Endocrinol Metab.2006 Jul;91 (7):2725-31. Epub 2006 Apr 24.
[17]Sethi JK, Vidal-Puig A. et al:Visfatin:the missing link between intra-abdominal obesity and diabetes? Trends Mol Med.2005 Aug; 11 (8):344-7.
[18]Van der Veer E, Nong Z, O'Neil C, et al. Pre-B-cell colony-enh-ancing factor regulates NAD+-dependent protein deaetylase activity and promotes vascular smooth muscle cell maturation. Circ Res 2005; 1:25-34.
[19]Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I. Cloning and characterization of the cDNA encoding a novel human pre-B cell colony-enhancing factor. Mol Cell Biol 1994; 14:1431-7.
[20]Jia SH, Li Y, Parodo J, Kapus A, Fan L, Rotstein OD, et al. Pre-Bcell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis. J Clin Invest 2004; 113:1318-27.
[21]Guerci B, Bohme P, Kearney-Schwartz A, Zannad F, Drouin P.:Diabetes Metab. Endothelial dysfunction and type 2 diabetes. Part 2:altered endothelial function and the effects of treatments in type 2 diabetes mellitus.2001 Sep; 27 (41):436-47.
[22]Lopez-Bermejo A, Chico-Julia B, Fernandez-Balsells M, Recasens M, Esteve E, Casamitjana R, et al. Serum visfatin increases with progressive beta-cell deterioration. Diabetes 2006;55:2871-5
[23]Dahl TB, Yndestad A, Skjelland M, Oie E, Michelsen A, Damas JK, et al. Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis:possible role in inflammation and plaque destabilization. Circulation 2007; 115:972-80.
[24]Moschen AR, Kaser A, Enrich B, et al:2007.Visfatin, an adipocyto -kine with proinflammatory and immunomodulating properties. J Immunol 178:1748-1758.
[25]Liu SW, Qiao SB, et al. Association of plasma visfatin levels with inflammation, atherosclerosis and acute coronary syndromes (ACS) in humans.[J].Clin Endocrinol (Oxf). 2009,71(2):202-7.
[26]Harper N, Hughes M, MacFarlane M, Cohen GM. Fas-associated death domain protein and caspase-8 are not recruited to the tumor necrosis factor receptor 1 signaling complex during tumor necrosis factor-induced apoptosis.J Biol Chem.2003 Jul 11; 278(28):25534-41. Epub 2003 Apr 29.
[27]Bazanova EA, Bukhova VP, Liampert IM. The role of non-type-specific protein antigens of the cell wall in Streptococcus group A in developing delayed hypersensitivity.Zh Mikrobiol Epidemiol Immunobiol.1987 Aug; (8):67-71.
[28]Baxter, G. T, Kuo, R. C, Jupp, O J, Vandenabeele, P.,& MacEwan, D. J (1999). Tumor necrosis factora mediates both apoptotic cell death and cell proliferation in a human hematopoietic cell line dependent on mitotic activity and receptor subtype expression. J Biol Chem274; 9539-9547.
[29]Li XQ, Zhao MG, Mei QB, Zhang YF, Guo W, Wang HF, Chen D, Cui Y. Effects of tumor necrosis factor-alpha on calcium movement in rat ventricular myocytes. Acta Pharmacol Sin.2003 Dec;24(12):1224-30.
[30]Harper N, Hughes M, MacFarlane M, Cohen GM. Fas-associated death domain protein and caspase-8 are not recruited to the tumor necrosis factor receptor 1 signaling complex during tumor necrosis factor-induced apoptosis.J Biol Chem.2003 Jul 11; 278(28):25534-41. Epub 2003 Apr 29.
[31]Beletsky IP, Moshnikova AB, Proussakova OV. Cytotoxic signal transduction pathways via TNF family receptors. Biochemistry (Mosc).2002 Mar; 67 (3):312-28.
[32]Sack, M. N., Smith, R. M.,& Opie, L. H. (2000). Tumor necrosis factor in myocardial hypertrophy and ischaemiaan anti-apoptotic perspective. Cardiovasc Res 45,688-695.
[33]Wang M, Tsai BM, Crisostomo PR, Meldrum DR. Tumor necrosis factor receptor 1 signaling resistance in the female myocardium during ischemia.Circulation.2006 Jul 4; 114: 282-9.
[34]Yasukawa H, Hoshijima M, Gu Y, Nakamura T, Pradervand S, et al:Suppressor of cytokine signaling-3 is a biomechanical stress -inducible gene that suppresses gp130-mediated cardiac myocyte hypertrophy and survival pathways. J Clin Invest.2001 Nov;108 (10):1459-67.
[35]Baines, C. P, Cohen, M. V,& Downey, J. M. (1999). Signal transduction in ischemic preconditioning:the role of kinases and Mitochondrial K(ATP) channels. J Cardiovasc Electrophysiol 10,741-754.
[36]Zechner, D., Craig, R., Hanford, D. S., McDonough, P. M., Sabbadini, R. A,& Glembotski, C. C. (1998). MKK6 activates myocardial cell NF-kappaB and inhibits apoptosis in a p38 mitogen-activated protein kinase-dependent manner. J Biol Chem 273,8232-8239.
[37]Lazou A, Sugden PH, Clerk A. Activation of mitogen-activated protein kinases (p38-MAPKs, SAPKs/JNKs and ERKs) by the G-protein-coupled receptor agonist phenylephrine in the perfused rat heart. Biochem J.1998 Jun 1; 332 (2):459-65.
[38]Haudek, S. B., Bryant, D. D.,& Giroir, B. P. (2001). Differential regulation of myocardial NF kappa B following acute or chronic TNF-alpha exposure. J Mol Cell Cardiol 33,1263-1271.
[39]Haunstetter, A.,& Izumo, S. (1998). Apoptosisbasic mechanisms and implications in cardiovascular disease. Circ Res 82,1111-1129.
[40]Wallach, D. (1997). Cell death induction by TNF:a matter of self control.Trends Biochem Sci 22,107-109.
[41]Bowden RA, Ding ZM, Donnachie EM, Petersen TK, Michael LH, Ballantyne CM, Burns AR. Role of alpha4 integrin and VCAM-1 in CD 18-independent neutrophil migration across mouse cardiac endothelium. Circ Res.2002 Mar 22; 90(5):562-9..
[42]Barath, P., Fishbein, M. C., Cao, J., Berenson, J., Helfant, R. H.,& Forrester, J. S. (1990). Detection and localization of tumor necrosis factor in human atheroma. Am J Cardiol 65, 297-302.
[43]Napoli, C., Quehenberger, O., De Nigris, F., Abete, P., Glass, C. K.,& Palinski, W. (2000). Mildly oxidized low density lipoprotein activates multiple apoptotic signaling pathways in human coronary cells. FASEB J14,1996-2007.
[44]Niemann-Jonsson, A., Dimayuga, P., Jovinge, S., Calara, F., Ares, M. P., Fredrikson, G. N., &Nilsson, J. (2000). Accumulation of LDL in ratarteries is associated with activation of tumor necrosis factor alpha expression. Arterioscler Thromb Vasc Biol 20,2205-2211.
[45]Binion DG, Rafiee P. Is inflammatory bowel disease a vascular disease? Targeting angiogenesis improves chronic inflammation in inflammatory bowel disease. Gastroenterology.2009 Feb; 136 (2):400-3. Epub 2008 Dec 26.
[46]Schonbeck U, Mach F, Sukhova GK, Murphy C, Bonnefoy JY, Fabunmi RP, Libby P. Regulation of matrix metalloproteinase expression in human vascular smooth muscle cells by T lymphocytes:a role for CD40 signaling in plaque rupture? Circ Res.1997 Sep; 81(3):448-54.
[47]Geng, Y. J., Wu, Q., Muszynski, M., Hansson, G K.,& Libby, P. (1996). Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta. Arterioscler Thromb Vasc Biol 16,19-27.
[48]Okura Y, Brink M, Itabe H, Scheidegger KJ, Kalangos A, Delafon -taine P. Oxidized low-density lipoprotein is associated with apoptosis of vascular smooth muscle cells in human atherosclerotic plaques Circulation.2000 Nov 28; 102(22):2680-6.
[49]Ferro, D., Parrotto, S., Basili, S., Alessandri, C.,& Violi, F. (2000) Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia. J Am Coll Cardiol 36427-431.
[50]Ridker, P. M., Rifai, N., Pfeffer, M. A., Sacks, F.,& Braunwald, E. (1999).Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation 100,230-235.
[51]Simes RJ, Marschner IC, Hunt D, Colquhoun D, Sullivan D, et al:Relationship between lipid levels and clinical outcomes in the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Trial:to what extent is the reduction in coronary events with pravastatin explained by on-study lipid levels?. Circulation.2002 Mar 12; 105(10):1162-9.
[52]Schieffer B, Biinte C, Witte J, Hoeper K, Boger RH, Schwedhelm E, Drexler H. Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease. J Am Coll Cardiol.2004 Jul 21; 44(2):362-8.
[53]Lee SK, Kim CS, Yang WS, Kim SB, Park SK, Park JS. Exogenous nitric oxide inhibits tumor necrosis factor-alpha or interleukin-1 beta-induced monocyte chemoattractant protein-1 expression in human mesangial cells. Role of IkappaB-alpha and cyclic GMP. Nephron.2002 Dec; 92(4):780-7.
[54]Kuzuya T, Nakagawa S, Satoh J, Kanazawa Y, Iwamoto Y, et al. Report of the Committee on the classification and diagnostic criteria of diabetes mellitus. Diabetes Res Clin Pract. 2002 Jan; 55(1):65-85.
[55]Patrik L,Vaessa Van H,Signy R,et al.Secretion of TNF-a shows a strong relationship to insulinstimulated gluose transport in human adipose tissue.Diabetes,2000; 49(5):688.
[56]Sarzi-Puttini P, Atzeni F, Shoenfeld Y, Ferraccioli G. TNF-alpha, rheumatoid arthritis, and heart failure:a rheumatological dilemma. Autoimmun Rev.2005 Mar; 4(3):153-61.
[57]Banfi C, Mussoni L, Tremoli E. PAI-1, the primary plasmatic inhibitor of fibrinolysis. Physiopathologic role and molecular mechan -isms. Minerva Endocrinol.2002 Sep; 27(3): 181-91.
[58]Aljada A,Ghanim H,Assian E,et al.TNF-α in hibits insulin induled increase in endothelial nitric oxide synthase and reduces insulinr-eceptor conteanphosphorylation.Metabolism, 2002;51(4):487.
[59]Sartippour MR, Renier G. Differential regulation of macrophage peroxisome proliferator-activated receptor expression by glucose:role of peroxisome proliferator-activated receptors in lipoprotein lipase gene expression. Arterioscler Thromb Vasc Biol.2000 Jan; 20(1):104-10.
[60]Mishima Y, Kuyama A, Tada A, Relationship between TNF-a and insulin resistance in obese men with T2DM.Diabetes Research Clinical Practice,2001;52 (2); 119.
[61]闫胜利,胰岛素抵抗与脂代谢异常。山东医药2003；43(13)：
[62]陈蕾,贾伟平,项坤三,葡萄糖嵌夹技术在糖尿病研究中的应用.中华内分泌代谢杂志,2003；19(1)：74-6.
[63]Mnttllews DR, HoskerJP, RudeI18kiAs, et al Homeostasis model assessment:insulin resistance and beta cell function from fasting plasma glucose and lnslllin concentration in man [J].Diabetoto-gia,1985,28(11):412-419
[64]Giovanni P, Pao10 G, Adriaan A, et al.Cardiac and skeletal muscle insulin resistance in patients with coronary heart disease [J]. Clin. invest.1996,98(11):2094-2099.
[65]Hrnciar J.. Amylin as an additional possible pathogenic factor in NIDDM and the insulin resistance syndrome [J]. Vnitr Lek.1996 Aug;42 (8):557-60.
[66]Hanley AJ, Williams K, Stern MP et al. Homeostasis modelasses -smentof insulin resistance in relation to the incidence of cardio-vascular disease:the San Antonio Heart Study. Diabetes Care 2002; 25(7):1177-1184.
[67]Pirro M, Mauriege P, Tchern of A, Cantin B. et al. Plasma free fatty acid levels and the risk of ischemic heart disease in men:prospective results from the Quebec Cardiovascular Study.Atherosclerosis.2002 Feb; 160(2):377-84.
[68]Pyorala K, Savolainen E, Kaukola S et al. Plasma insulin as coronary heart disease risk factor:relationship to other risk factors and predictive value during 91/2-year follow-up of the Helsinki Policemen Study population. Acta Medica Scandinavica. Supplemen-turn 1985; 701:38-52.
[69]Ducimetiere P, Eschwege E, Papoz L et al. Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population. Diabetologia 1980; 19(3):205-210.
[70]Nystrom T. The potential beneficial role of glucagon-like peptide-1 in endothelial dysfunction and heart failure associated with insulin resistance. Horm Metab Res.2008 Sep; 40(9):593-606. Epub 2008 Sep 15.
[71]Arnal JF, Dinh-Xuan AT, Pueyo M, Darblade B, Rami J.Endothelium-derived nitric oxide and vascular physiology and pathology. Cell Mol Life Sci.1999 Jul; 55(8-9):1078-87.
[72]Potenza MA, Marasciulo FL, Chieppa DM et al. Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production. American Journal of Physiology. Heart and Circulatory Physiology 2005; 289(2):H813-H822.
[73]Peppa M, Vlassara H. Advanced glycation end products and diabetic complications:a general overview. Hormones (Athens).2005 Jan-Mar; 4(1):28-37.
[74]Iozzo P, Chareonthaitawee P, Rimoldi O, et al. Mismatch between insulin-mediated glucose uptake and blood flow in the heart of patients with Type Ⅱ diabetes. Diabetologia.2002 Oct; 45(10):1404-9. Epub 2002 Jul 27.
[75]Natali A, Buzzigoli G, Taddei S, Santoro D, Cerri M, Pedrinelli R, Ferrannini E. Effects of insulin on hemodynamics and metabolism in human forearm. Diabetes.1990 Apr; 39(4):490-500.
[76]Sondergaard HM, Bottcher M, Marie Madsen M, et al. Impact of type 2 diabetes on myocardial insulin sensitivity to glucose uptake and perfusion in patients with coronary artery disease. J Clin Endocrinol Metab.2006 Dec; 91(12):4854-61. Epub 2006 Sep 19.
[77]Paternostro G, Camici PG, Lammerstma AA, et al. Cardiac and skeletal muscle insulin resistance in patients with coronary heart disease. A study with positron emission tomography. J Clin Invest 1996;98(November (9)):2094-9.
[78]Pagano C, Pilon C, Olivieri M, Mason P, Fabris R, et al. Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to insulin resistance in humans.. J Clin Endocrinol Metab.2006 Aug; 91(8):3165-70. Epub 2006 May 23.
[79]Krzyzanowska K, Krugluger W, Mittermayer F, Rahman R, Haider D, Shnawa N, Schernthaner G. Increased visfatin concentrations in women with gestational diabetes mellitus. Clin Sci (Lond).2006 May; 110(5):605-9.
[80]Lamarche B, Tchernof A, Mauriege P, Cantin B, Dagenais GR, Lupien PJ, Despres JP. Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease. JAMA.1998 Jun 24; 279(24):1955-61.
[1]Fantuzzi G., Adipose tissue, adipokines, and inflammation[J].J Aller-gy Clin.Immunol, 2005,115:911-919.
[2]Fukuhara A, Matsuda M, Nishizawa M, et al. Visfatin:a protein secreted by visceral fat that mimics the effects of insulin [J]. Science,2005,307:426-430.
[3]Sethi JK, Vidal2 Puig A. Visfatin:the missing link between intra-abdominal obesity and diabetes? Trends Mol Med,2005,11:344-347.
[4]J ia S H, Li Y, Par odo J, et al. Pre2 B cell col ony2 enhancing factor inhibits neutrophil apoptosis in experi mental inflammati on and clinical sepsis [J]. J Clin Invest,2004,113 (9): 1318-1327.
[5]Bajwa EK, Yu CL, Gong MN, Thompson BT, Christiani DC. Pre-B-cellcolony-enhancing factor gene polymorphisms and risk of acute respiratory distress syndrome. Crit Care Med. 2007 May; 35 (5):1290-5.
[6]Berndt J, Kloting N, Kralisch S,et al. Plasma visfatin concen-trations and fat depot-specific mRNA expression in humans. Diabetes 2005; 54:2911-2916.
[7]Jia SH, Li Y, Parodo J, et al. Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis. J Clin Invest 2004; 113:1318-1327.
[8]Ognjanovic S, Bao S, Yamamoto S Y, et al. Genomic organization of the gene coding for human p re2 B2 cell colony enhancing facto and expressi on in human fetal membranes[J]. J Mol Endocrinol 2001,26 (2):1072-117.
[9]Samal B, Sun Y, Stearns G, et al. Cloning and characterizati on of the cDNA encoding a novel human p re2 B2 cell colony-enhancing factor [J]. Mol Cell Biol,1994,14 (2):14312 1437:
[10]Steppan CM, Wang J, Whiteman EL,et al.Activation of SOCS-3 by resistin.Mol Cell Biol,2005,25:1569-1575
[11]Banerjee RR, Rangwala SM, Shapiro JS, et al.Regulation of fasted blood glucose by resistin,Science,2004,303:1195-1198.
[12]Sato N, Kobayashi K, Inoguchi T, et al.Adenovinus-mediated high expression of resistin causes dyslipidemia in mice.Endocrinology,2005,146:273-279.
[13]Satoh H,Nguyen MT,Miles PD, et al.Adenovirus-mediated chronic " hyperresistinemia" leads to in vivo insulin resistance in normal rats.J Clin Invest,2004,114:224-231.
[14]Moon B,Kwan JJ,Duddy N,et al.Resistin inhibits glucose uptake in L6 cells independently of changes in insulin signaling and GLUT4 translocation.Am J Endocrinol Metab,2003,285:E106-E115.
[15]ChenMP, Chung FM,Chang D M, et al,Elevated plasma level of visfatin/Pre-B cell colony-enhancing factor in patients with type 2 diabets.J Clin Endocrinol Metab,2006,Jan, 91(1):295-299
[16]Yoshinor,Archana,Masafumi,et al.Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic pati-ents.The Journal of Clinical Endocrinology & Metabolis-m,2005,87(6):2784-2791.
[17]Choi KC, Ryu OH, Lee KW, et al. Effect of PPAR-alpha and-gamma agonist on the expression of visfatin, adiponectin, and TNF-alpha in visceral fat of OLETF rats. Biochem Biophys Res Commun 2005;
[18]Hammarstedt A, Pihlajamaki J, Rotter SopasakisV, et al. Visfatin is an adi pokine but it is not regulated by thiazolidinedi ones. J Clin EndocrinolMetab,2006,91:1181-1184
[19]Gaber T, Dziurla R, TschirschmannM, et al. The effect of hypoxia on the exp ression of pbef in CD4+Lymphocytes[J]. Ann Rheum Dis,2006,65 (6):455.
[20]Bae S K, Kim S R, Kim J G, et al. Hypoxic inducti on of human visfatin gene is directly mediated by hypoxia2inducible factor 1[J]. FEBS Lett,2006,580 (17):41052 4113.
[21]Frydelund2 Larsen L, Akerstrom T, Nielsen S, et al. Visfatin mRNA exp ressi on in human subcutaneous adi pose tissue is regulated by exercise [J]. Am J Physiol EndocrinolMetab, 2007,292(1):E242-31.
[22]Kralisch S, Klein J, Lossner U, et al. Isoproterenol, TNFalpha, and insulin downregulate adipose triglyceride lipase in 3T3-L1 adipocytes. Mol Cell Endocrinol 2005; 240:43-49.
[23]Arner P. Visfatin2 A true or false trail t o type 2 diabetes mellitus [J]. J Clin EndocrinolMetab,2006,91 (1):28230.
[24]Kralisch S, Klein J, Lossner U, et al. Interleukin-6 is a negative regulator of visfatin gene expression in 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab 2005; 289:E586-E590.
[25]Patr one L, DamoreaM A, LeeM B, et al. Genes exp ressed during the IFNy-induced maturation of pre-B cells [J]. Mol I mmunol,2001,38 (8):5972 606.
[26]Haider DG, Plenier J, Francesconi M,et al.Exercise training lowers plasma visfatin concentrations in patients with type 1 diabetes [J].J Clin Endocrinol Metab,2006,91(11): 4702-4704.
[27]Steppan CM,Bailey ST,Bhat S,et al.The hormone resistin links obesity to diabetes. Nature, 2001,409:307-312.
[28]ChenMP, Chung FM, Chang DM, et al. Elevated plasma level of visfatin/Pre-B cell col-onyenhancing fact or in pa-tients with type 2 diabetes mellitus. J Clin Endocrinol Metab, 2006,91:295-299.
[29]Lopez-Bermejo A,Chico-Julia B,Fernandez-Balsells M,et al.Serum visfatin increase with progressive{beta}-cell deterioration [J].Diabetes,2006,55(10):2871-2875
[30]Dogru T,Sonmez A, Tasci I, et al.Plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabets mellitus and impaired glucose tolerance[J]. Diabetes Res Clin Pract,2007,76 (1):24-29
[31]Krzyzanowska K, Krugluger W, Mittermayer F, et al.Increased visfatin concentrations in women with gestational diabetes mellitus[J]. Clin Sci (Lond),2006,110 (5):605-609.
[32]Kitani T, Okuno S, Fujisawa H. Growth phase-dependent changes in the subcellular localization of pre-B cell colony-enhancing factor. FEBS Lett 2003; 544:74-78.
[33]Cinti S, Mitchell G, Barbatelli G, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46:2347-2355.
[34]Haider DG, Schindler K, Schaller G, et al. Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding [J].J Clin Endocrinol Metab, 2006,91(4):1578-1581.
[35]Pagano C,Pilon C,Olivieri M,et al. Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to insulin resistance in humans [J].J Clin Endocrinol Metab,2006,91 (8):3165-3170
[36]Kloting N, Kloting I. Visfatin:gene expression in isolated adipocytes and sequence analysis in obese WOKW rats compared with lean control rats. Biochem Biophys Res Commun 2005; 332:1070-1072.
[37]Samal B, Sun Y, Stearns G, et al. Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol Cell Biol 1994; 14:1431-1437.
[38]McGlothlin JR, Gao L, Lavoie T, Simon BA, Easley RB, et al. Molecular cloning and characterization of canine pre-B-cell colony-enhancing factor. Biochem Genet.2005 Apr; 43(3-4):127-41.
[39]Van der Veer E, Nong Z, O'Neil C, et al. Pre-B-cell colony-enhancing factor regulates NAD+dependent protein deacetylase activity and promotes vascular smooth muscle cell maturation. Circ Res 2005; 1:25-34.
[40]Haider DG, Schindler K,Schaller G, cr al. Increased plasma level visfatin concentrations in morbidly obese subjects are reduced after gastric banding[J].J Clin Endocrinol Metab, 2005,91:3165-3170.
[41]Schindler K,Haider D,Wolzt M,et al.Impact of anti-retroviral therapy on visfatin and retinol-binding protein 4 in HIV-infected subjects[J].Eur J Clin Invest,2006,36(9):640-646.
[42]Bemdt J, Kloting N, Kralisch S, et at.Plasma visfatin concentrat-ions and fat depet-specific mRNA expresson in humans [J]. Diabetes,2005,54(10):2911-2916.
[43]Moschen AR,Kaser A,Enrich B,et al. Visfatin,an adipocytokine with proinflammatory and immunomodulating properties[J].J Immunol,2007,178(3):1748-1758.
[44]Dahl TB, Yndestad A, Skjelland M. Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis:possible role in inflammation and plaque destabilization [J].Circulation,2007,115(8):972-980.
[45]Liu SW, Qiao SB, et al. Association of plasma visfatin levels with inflammation, atherosclerosis and acute coronary syndromes (ACS) in humans. [J].Clin Endocrinol (Oxf). 2009,71(2):202-7.
[46]Pillai JB, Isbatan A ImaiS,et al. Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2a deacetylase activity[J].J Biol Chem,2005,280:43121-43130
[47]Ye SQ, Zhang LQ, Adyshev D, et al. Pre-B-cell-colony-enhancing factor is critically involved in thrombin-induced lung endothelial cell barrier dysregulation. Microvasc Res. 2005; Sep 23 [Epub ahead of print].
[48]Ognjanovic S, Bryant-Greenwood GD. Pre-B-cell colony-enhancing factor, a novel cytokine of human fetal membranes. Am J Obstet Gynecol 2002; 187:1051-1058.
[49]Rongvaux A, Shea RJ, Mulks MH, et al. Pre-B-cell colony-enhancing factor, whose expression is upregulated in activated lymphocytes, is a nicotinamide phosphoribosyl transferase, a cytosolic enzyme involved in NAD biosynthesis. Eur J Immunol 2002; 11:3225-3234.