转化生长因子β1与心血管疾病的研究进展
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摘要
转化生长因子β1(transforming growth factorβ1,TGF-β1)是TGF-β超家族成员之一,是调节细胞生长、促进组织纤维化的重要细胞因子。研究发现TGF-β1多在血管平滑肌细胞、内皮细胞、造血细胞和巨噬细胞中表达,在高血压、冠心病、心力衰竭、心房纤颤等众多心血管疾病中起至关重要的作用。
Transforming growth factor β1(TGF-β1) is a member of the TGF-β superfamily and is an important cytokine that regulates cell growth and promotes tissue fibrosis. It has been found that TGF-β1 is expressed in vascular smooth muscle cells, endothelial cells, hematopoietic and macrophages cells, and plays a very important role in many cardiovascular diseases such as hypertension, coronary heart disease, heart failure and atrial fibrillation.
Transforming growth factor β1(TGF-β1) is a member of the TGF-β superfamily and is an important cytokine that regulates cell growth and promotes tissue fibrosis. It has been found that TGF-β1 is expressed in vascular smooth muscle cells, endothelial cells, hematopoietic and macrophages cells, and plays a very important role in many cardiovascular diseases such as hypertension, coronary heart disease, heart failure and atrial fibrillation.
引文
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2.Nakao E,Adachi H,Enomoto M,et al.Elevated plasma transforming growth factor beta1 levels predict the development of hypertension in normotensives:the 14-year follow-up study[J].Am J Hypertens,2017,30(8):808-814.
3.Chen HJ,Mo N,Zhang YF,et al.Role of gene polymorphisms/haplotypes and plasma level of TGF-beta1 in susceptibility to instent restenosis following coronary implantation of bare metal stent in chinese Han patients[J].Int Heart J,2018,59(1):161-169.
4.Mancini D,Monteagudo J,Suarez-Farinas M,et al.New methodologies to accurately assess circulating active transforming growth factor-beta1levels:implications for evaluating heart failure and the impact of left ventricular assist devices[J].Transl Res,2018,192:15-29.
5.Feizollahzadeh S,Taheripanah R,Khani M,et al.Promoter region polymorphisms in the transforming growth factor beta-1(TGFbeta1)gene and serum TGFbeta1 concentration in preeclamptic and control Iranian women[J].J Reprod Immunol,2012,94(2):216-221.
6.Yan Y,Wang XJ,Li SQ,et al.Elevated levels of plasma transforming growth factor-beta1 in idiopathic and heritable pulmonary arterial hypertension[J].Int J Cardiol,2016,222:368-374.
7.Vieira de Castro J,Gon?alves CS,Costa S,et al.Impact of TGF-beta1-509C/T and 869T/C polymorphisms on glioma risk and patient prognosis[J].Tumour Biol,2015,36(8):6525-6532.
8.Hara T,Yoshida E,Fujiwara Y,et al.Transforming growth factor-beta1modulates the expression of syndecan-4 in cultured vascular endothelial cells in a biphasic manner[J].J Cell Biochem,2017,118(8):2009-2017.
9.Park S,Lee S,Park EJ,et al.TGFbeta1 induces stress fiber formation through upregulation of TRPC6 in vascular smooth muscle cells[J].Biochem Biophys Res Commun,2017,483(1):129-134.
10.Mohy A,Fouad A.Role of transforming growth factor-beta1 in serum and-509 C>T promoter gene polymorphism in development of liver cirrhosis in Egyptian patients[J].Meta Gene,2014,2:631-637.
11.Rath D,Chatterjee M,Holtkamp A,et al.Evidence of an interaction between TGF-beta1 and the SDF-1/CXCR4/CXCR7 axis in human platelets[J].Thromb Res,2016,144:79-84.
12.Koehler L,Samsonov S,Rother S,et al.Sulfated hyaluronan derivatives modulate TGF-beta1:receptor complex formation:possible consequences for TGF-beta1 signaling[J].Sci Rep,2017,7(1):1210.
13.di Clemente N,Jamin S P,Lugovskoy A,et al.Processing of antiMullerian hormone regulates receptor activation by a mechanism distinct from TGF-beta[J].Mol Endocrinol,2010,24(11):2193-2206.
14.Zhang L,Han C,Ye F,et al.Plasma gelsolin induced glomerular fibrosis via the TGF-beta1/Smads signal transduction pathway in IgAnephropathy[J].Int J Mol Sci,2017,18(2):E390.
15.Re RN.A proposed mechanism for the Berecek phenomenon with implications for cardiovascular reprogramming[J].J Am Soc Hypertens,2018,12(9):644-651.
16.Pinto YM,Pinto-Sietsma SJ,Philipp T,et al.Reduction in left ventricular messenger RNA for transforming growth factor beta(1)attenuates left ventricular fibrosis and improves survival without lowering blood pressure in the hypertensive TGR(mRen2)27 Rat[J].Hypertension,2000,36(5):747-754.
17.Li B,Khanna A,Sharma V,et al.TGF-beta1 DNA polymorphisms,protein levels,and blood pressure[J].Hypertension,1999,33(1 Pt 2):271-275.
18.Guo D,Shen C,Chen Y,et al.Polymorphisms of the TGFBRAP1 gene in relation to blood pressure variability and plasma TGF-beta1[J].Clin Exp Hypertens,2015,37(5):420-425.
19.He F,Zhao D,Deng F,et al.Association of TGF-beta1 gene p o l y m o r p h i s m s i n e x o n 1 a n d b l o o d l e v e l s w i t h e s s e n t i a l hypertension[J].Blood Press,2010,19(4):225-233.
20.刘鹏,王德宝,张凤梅,等.替米沙坦对早期糖尿病肾病患者血浆同型半胱氨酸及转化生长因子β1水平的影响[J].中华全科医师杂志,2012,11(8):611-613.LIU Peng,WANG Debao,ZHANG Fengmei,et al.Effects of telmisartan on plasma homocysteine and transforming growth factorβ1levels in patients with early diabetic nephropathy[J].Chinese Journal of General Practitioners,2012,11(8):611-613.
21.Grossman C,Levin M,Koren-Morag N,et al.Left ventricular hypertrophy predicts cardiovascular events in hypertensive patients with coronary artery calcifications[J].Am J Hypertens,2018,31(3):313-320.
22.李佳莘,朱晓雨,鲁美丽,等.电针与黄芪甲苷结合对大鼠心肌纤维化的影响[J].针刺研究,2017,42(6):477-481.LI Jiashen,ZHU Xiaoyu,LU Meili,et al.Effect of combined intervention of electroacupuncture and astragaloside IV on myocardial hypertrophy and TGF-β1/Smad signaling in rats with myocardial fibrosis[J].Acupuncture Research,2017,42(6):477-481.
23.Petrov VV,Fagard RH,Lijnen PJ.Stimulation of collagen production by transforming growth factor-beta1 during differentiation of cardiac fibroblasts to myofibroblasts[J].Hypertension,2002,39(2):258-263.
24.郑婧.自发性高血压大鼠心肌组织microRNA-97a与TGF-β1蛋白表达的改变及意义[J].中国比较医学杂志,2016,26(11):72-76.ZHENG Jing.Changes and significance of microRNA-97a and TGF-β1protein expression in myocardial tissue of spontaneously hypertensive rats[J].Chinese Journal of Comparative Medicine,2016,26(11):72-76.
25.Liu RM,Gaston PK.Oxidative stress and glutathione in TGF-betamediated fibrogenesis[J].Free Radic Biol Med,2010,48(1):1-15.
26.张娟娟.转化生长因子β1和结缔组织生长因子与高血压左心室肥厚的相关性[J].社区医学杂志,2017,15(22):1-4.ZHANG Juanjuan.Correlation between transforming growth factorβ1and connective tissue growth factor and left ventricular hypertrophy in hypertension[J].Journal of Community Medicine,2017,15(22):1-4.
27.Benjamin EJ,Virani SS,Callaway CW,et al.Heart disease and stroke statistics-2018 update:a report from the American heart association[J].Circulation,2018,137(12):e67-e492.
28.Cochain C,Zernecke A.Macrophages in vascular inflammation and atherosclerosis[J].Pflugers Arch,2017,469(3/4):485-499.
29.Kotlarz D,Marquardt B,Baroy T,et al.Human TGF-beta1 deficiency causes severe inflammatory bowel disease and encephalopathy[J].Nat Genet,2018,50(3):344-348.
30.张艳,李志樑,胡春玲.急性冠状动脉综合征患者m TOR活化与调节性T细胞及细胞因子的关系[J].天津医药,2015,43(4):416-418.ZHANG Yan,LI Zhiliang,HU Chunling.Relationship between mTORactivation and regulatory T cells and cytokines in patients with acute coronary syndrome[J].Tianjin Medical Journal,2015,43(4):416-418.
31.苗玉梅.冠心病患者血清转化生长因子-β1与肝细胞生长因子的相关性[J].中国老年学杂志,2015,35(23):6730-6731.MIAO Yumei.Correlation between serum transforming growth factor-β1 and hepatocyte growth factor in patients with coronary heart disease[J].Chinese Journal of Gerontology,2015,35(23):6730-6731.
32.寇民生,耿丽群,耿爱群.转化生长因子β1在不同程度冠状动脉粥样硬化中表达变化的意义[J].中西医结合心脑血管病杂志,2018,16(5):660-661.KOU Minsheng,GENG Liqun,GENG Aiqun.Significance of transforming growth factorβ1 expression in different degrees of coronary atherosclerosis[J].Chinese Journal of Integrative Medicine on Cardio-/Cerebrovascular Disease,2018,16(5):660-661.
33.王洁妤,华琦.左心室射血分数保留的心力衰竭研究进展[J].中华老年心脑血管病杂志,2016,18(7):766-769.WANG Jieyu,HUA Qi.Progress in heart failure with left ventricular ejection fraction retention[J].Chinese Journal of Geriatric Cardiovascular and Cerebrovascular Diseases,2016,18(7):766-769.
34.Morine KJ,Qiao X,York S,et al.Bone morphogenetic protein 9reduces cardiac fibrosis and improves cardiac function in heart failure[J].Circulation,2018,[Epub ahead of print].
35.Wang W,Wang C,Li L,et al.Inhibition of TGF-beta1 might be a novel therapeutic target in the treatment of cardiac fibrosis[J].Int J Cardiol,2018,256:19.
36.Chen L,Yan KP,Liu XC,et al.Valsartan regulates TGF-beta/Smads and TGF-beta/p38 pathways through lncRNA CHRF to improve doxorubicin-induced heart failure[J].Arch Pharm Res,2018,41(1):101-109.
37.Chen K,Chen W,Liu SL,et al.Epigallocatechin gallate attenuates myocardial injury in a mouse model of heart failure through TGFbeta1/Smad3 signaling pathway[J].Mol Med Rep,2018,17(6):7652-7660.
38.陈万,李佑美,首云锋.左室舒张功能衰竭患者NF-κB和TGF-β1与心室重构的相关性分析[J].海南医学院学报,2017,23(3):313-315.CHEN Wan,LI Youmei,SHOU Yunfeng.Correlation between NF-κBand TGF-β1 and ventricular remodeling in patients with left ventricular diastolic failure[J].Journal of Hainan Medical College,2017,23(3):313-315.
39.Sun Y,Huang ZY,Wang ZH,et al.TGF-beta1 and TIMP-4 regulate atrial fibrosis in atrial fibrillation secondary to rheumatic heart disease[J].Mol Cell Biochem,2015,406(1/2):131-138.
40.Cochet H,Scherr D,Zellerhoff S,et al.Atrial structure and function 5years after successful ablation for persistent atrial fibrillation:an MRIstudy[J].J Cardiovasc Electrophysiol,2014,25(7):671-679.
41.易懿,刘旭.心房纤维化机制的研究进展[J].国际心血管病杂志,2018,45(3):146-148.YI Yi,LIU Xu.Research progress in atrial fibrosis mechanism[J].International Journal of Cardiology,2018,45(3):146-148.
42.Verheule S,Sato T,Everett TT,et al.Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1[J].Circ Res,2004,94(11):1458-1465.
43.Rahmutula D,Marcus GM,Wilson EE,et al.Molecular basis of selective atrial fibrosis due to overexpression of transforming growth factor-beta1[J].Cardiovasc Res,2013,99(4):769-779.
44.Zhang D,Liu X,Chen X,et al.Role of the MAPKs/TGF-beta1/TRAF6 signaling pathway in atrial fibrosis of patients with chronic atrial fibrillation and rheumatic mitral valve disease[J].Cardiology,2014,129(4):216-223.
2.Nakao E,Adachi H,Enomoto M,et al.Elevated plasma transforming growth factor beta1 levels predict the development of hypertension in normotensives:the 14-year follow-up study[J].Am J Hypertens,2017,30(8):808-814.
3.Chen HJ,Mo N,Zhang YF,et al.Role of gene polymorphisms/haplotypes and plasma level of TGF-beta1 in susceptibility to instent restenosis following coronary implantation of bare metal stent in chinese Han patients[J].Int Heart J,2018,59(1):161-169.
4.Mancini D,Monteagudo J,Suarez-Farinas M,et al.New methodologies to accurately assess circulating active transforming growth factor-beta1levels:implications for evaluating heart failure and the impact of left ventricular assist devices[J].Transl Res,2018,192:15-29.
5.Feizollahzadeh S,Taheripanah R,Khani M,et al.Promoter region polymorphisms in the transforming growth factor beta-1(TGFbeta1)gene and serum TGFbeta1 concentration in preeclamptic and control Iranian women[J].J Reprod Immunol,2012,94(2):216-221.
6.Yan Y,Wang XJ,Li SQ,et al.Elevated levels of plasma transforming growth factor-beta1 in idiopathic and heritable pulmonary arterial hypertension[J].Int J Cardiol,2016,222:368-374.
7.Vieira de Castro J,Gon?alves CS,Costa S,et al.Impact of TGF-beta1-509C/T and 869T/C polymorphisms on glioma risk and patient prognosis[J].Tumour Biol,2015,36(8):6525-6532.
8.Hara T,Yoshida E,Fujiwara Y,et al.Transforming growth factor-beta1modulates the expression of syndecan-4 in cultured vascular endothelial cells in a biphasic manner[J].J Cell Biochem,2017,118(8):2009-2017.
9.Park S,Lee S,Park EJ,et al.TGFbeta1 induces stress fiber formation through upregulation of TRPC6 in vascular smooth muscle cells[J].Biochem Biophys Res Commun,2017,483(1):129-134.
10.Mohy A,Fouad A.Role of transforming growth factor-beta1 in serum and-509 C>T promoter gene polymorphism in development of liver cirrhosis in Egyptian patients[J].Meta Gene,2014,2:631-637.
11.Rath D,Chatterjee M,Holtkamp A,et al.Evidence of an interaction between TGF-beta1 and the SDF-1/CXCR4/CXCR7 axis in human platelets[J].Thromb Res,2016,144:79-84.
12.Koehler L,Samsonov S,Rother S,et al.Sulfated hyaluronan derivatives modulate TGF-beta1:receptor complex formation:possible consequences for TGF-beta1 signaling[J].Sci Rep,2017,7(1):1210.
13.di Clemente N,Jamin S P,Lugovskoy A,et al.Processing of antiMullerian hormone regulates receptor activation by a mechanism distinct from TGF-beta[J].Mol Endocrinol,2010,24(11):2193-2206.
14.Zhang L,Han C,Ye F,et al.Plasma gelsolin induced glomerular fibrosis via the TGF-beta1/Smads signal transduction pathway in IgAnephropathy[J].Int J Mol Sci,2017,18(2):E390.
15.Re RN.A proposed mechanism for the Berecek phenomenon with implications for cardiovascular reprogramming[J].J Am Soc Hypertens,2018,12(9):644-651.
16.Pinto YM,Pinto-Sietsma SJ,Philipp T,et al.Reduction in left ventricular messenger RNA for transforming growth factor beta(1)attenuates left ventricular fibrosis and improves survival without lowering blood pressure in the hypertensive TGR(mRen2)27 Rat[J].Hypertension,2000,36(5):747-754.
17.Li B,Khanna A,Sharma V,et al.TGF-beta1 DNA polymorphisms,protein levels,and blood pressure[J].Hypertension,1999,33(1 Pt 2):271-275.
18.Guo D,Shen C,Chen Y,et al.Polymorphisms of the TGFBRAP1 gene in relation to blood pressure variability and plasma TGF-beta1[J].Clin Exp Hypertens,2015,37(5):420-425.
19.He F,Zhao D,Deng F,et al.Association of TGF-beta1 gene p o l y m o r p h i s m s i n e x o n 1 a n d b l o o d l e v e l s w i t h e s s e n t i a l hypertension[J].Blood Press,2010,19(4):225-233.
20.刘鹏,王德宝,张凤梅,等.替米沙坦对早期糖尿病肾病患者血浆同型半胱氨酸及转化生长因子β1水平的影响[J].中华全科医师杂志,2012,11(8):611-613.LIU Peng,WANG Debao,ZHANG Fengmei,et al.Effects of telmisartan on plasma homocysteine and transforming growth factorβ1levels in patients with early diabetic nephropathy[J].Chinese Journal of General Practitioners,2012,11(8):611-613.
21.Grossman C,Levin M,Koren-Morag N,et al.Left ventricular hypertrophy predicts cardiovascular events in hypertensive patients with coronary artery calcifications[J].Am J Hypertens,2018,31(3):313-320.
22.李佳莘,朱晓雨,鲁美丽,等.电针与黄芪甲苷结合对大鼠心肌纤维化的影响[J].针刺研究,2017,42(6):477-481.LI Jiashen,ZHU Xiaoyu,LU Meili,et al.Effect of combined intervention of electroacupuncture and astragaloside IV on myocardial hypertrophy and TGF-β1/Smad signaling in rats with myocardial fibrosis[J].Acupuncture Research,2017,42(6):477-481.
23.Petrov VV,Fagard RH,Lijnen PJ.Stimulation of collagen production by transforming growth factor-beta1 during differentiation of cardiac fibroblasts to myofibroblasts[J].Hypertension,2002,39(2):258-263.
24.郑婧.自发性高血压大鼠心肌组织microRNA-97a与TGF-β1蛋白表达的改变及意义[J].中国比较医学杂志,2016,26(11):72-76.ZHENG Jing.Changes and significance of microRNA-97a and TGF-β1protein expression in myocardial tissue of spontaneously hypertensive rats[J].Chinese Journal of Comparative Medicine,2016,26(11):72-76.
25.Liu RM,Gaston PK.Oxidative stress and glutathione in TGF-betamediated fibrogenesis[J].Free Radic Biol Med,2010,48(1):1-15.
26.张娟娟.转化生长因子β1和结缔组织生长因子与高血压左心室肥厚的相关性[J].社区医学杂志,2017,15(22):1-4.ZHANG Juanjuan.Correlation between transforming growth factorβ1and connective tissue growth factor and left ventricular hypertrophy in hypertension[J].Journal of Community Medicine,2017,15(22):1-4.
27.Benjamin EJ,Virani SS,Callaway CW,et al.Heart disease and stroke statistics-2018 update:a report from the American heart association[J].Circulation,2018,137(12):e67-e492.
28.Cochain C,Zernecke A.Macrophages in vascular inflammation and atherosclerosis[J].Pflugers Arch,2017,469(3/4):485-499.
29.Kotlarz D,Marquardt B,Baroy T,et al.Human TGF-beta1 deficiency causes severe inflammatory bowel disease and encephalopathy[J].Nat Genet,2018,50(3):344-348.
30.张艳,李志樑,胡春玲.急性冠状动脉综合征患者m TOR活化与调节性T细胞及细胞因子的关系[J].天津医药,2015,43(4):416-418.ZHANG Yan,LI Zhiliang,HU Chunling.Relationship between mTORactivation and regulatory T cells and cytokines in patients with acute coronary syndrome[J].Tianjin Medical Journal,2015,43(4):416-418.
31.苗玉梅.冠心病患者血清转化生长因子-β1与肝细胞生长因子的相关性[J].中国老年学杂志,2015,35(23):6730-6731.MIAO Yumei.Correlation between serum transforming growth factor-β1 and hepatocyte growth factor in patients with coronary heart disease[J].Chinese Journal of Gerontology,2015,35(23):6730-6731.
32.寇民生,耿丽群,耿爱群.转化生长因子β1在不同程度冠状动脉粥样硬化中表达变化的意义[J].中西医结合心脑血管病杂志,2018,16(5):660-661.KOU Minsheng,GENG Liqun,GENG Aiqun.Significance of transforming growth factorβ1 expression in different degrees of coronary atherosclerosis[J].Chinese Journal of Integrative Medicine on Cardio-/Cerebrovascular Disease,2018,16(5):660-661.
33.王洁妤,华琦.左心室射血分数保留的心力衰竭研究进展[J].中华老年心脑血管病杂志,2016,18(7):766-769.WANG Jieyu,HUA Qi.Progress in heart failure with left ventricular ejection fraction retention[J].Chinese Journal of Geriatric Cardiovascular and Cerebrovascular Diseases,2016,18(7):766-769.
34.Morine KJ,Qiao X,York S,et al.Bone morphogenetic protein 9reduces cardiac fibrosis and improves cardiac function in heart failure[J].Circulation,2018,[Epub ahead of print].
35.Wang W,Wang C,Li L,et al.Inhibition of TGF-beta1 might be a novel therapeutic target in the treatment of cardiac fibrosis[J].Int J Cardiol,2018,256:19.
36.Chen L,Yan KP,Liu XC,et al.Valsartan regulates TGF-beta/Smads and TGF-beta/p38 pathways through lncRNA CHRF to improve doxorubicin-induced heart failure[J].Arch Pharm Res,2018,41(1):101-109.
37.Chen K,Chen W,Liu SL,et al.Epigallocatechin gallate attenuates myocardial injury in a mouse model of heart failure through TGFbeta1/Smad3 signaling pathway[J].Mol Med Rep,2018,17(6):7652-7660.
38.陈万,李佑美,首云锋.左室舒张功能衰竭患者NF-κB和TGF-β1与心室重构的相关性分析[J].海南医学院学报,2017,23(3):313-315.CHEN Wan,LI Youmei,SHOU Yunfeng.Correlation between NF-κBand TGF-β1 and ventricular remodeling in patients with left ventricular diastolic failure[J].Journal of Hainan Medical College,2017,23(3):313-315.
39.Sun Y,Huang ZY,Wang ZH,et al.TGF-beta1 and TIMP-4 regulate atrial fibrosis in atrial fibrillation secondary to rheumatic heart disease[J].Mol Cell Biochem,2015,406(1/2):131-138.
40.Cochet H,Scherr D,Zellerhoff S,et al.Atrial structure and function 5years after successful ablation for persistent atrial fibrillation:an MRIstudy[J].J Cardiovasc Electrophysiol,2014,25(7):671-679.
41.易懿,刘旭.心房纤维化机制的研究进展[J].国际心血管病杂志,2018,45(3):146-148.YI Yi,LIU Xu.Research progress in atrial fibrosis mechanism[J].International Journal of Cardiology,2018,45(3):146-148.
42.Verheule S,Sato T,Everett TT,et al.Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1[J].Circ Res,2004,94(11):1458-1465.
43.Rahmutula D,Marcus GM,Wilson EE,et al.Molecular basis of selective atrial fibrosis due to overexpression of transforming growth factor-beta1[J].Cardiovasc Res,2013,99(4):769-779.
44.Zhang D,Liu X,Chen X,et al.Role of the MAPKs/TGF-beta1/TRAF6 signaling pathway in atrial fibrosis of patients with chronic atrial fibrillation and rheumatic mitral valve disease[J].Cardiology,2014,129(4):216-223.