心肌胶原代谢标志物血清水平与不同类型房颤的相关性研究
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摘要
目的心房颤动(Atrial fibrillation,Af)简称房颤,其发生及维持机制与心房结构重构和电重构有关。心房结构重构促进促进激动各向异性传导,使得心肌细胞间偶联异质性增加,缩短波长的不定向阻滞,有利于折返机制的形成,从而促使房颤的发生及维持;心肌纤维化(myocardial fibrosis,MF)是心房结构重构的主要表现,是心肌细胞外基质(extracellular matrix,ECM)重构的病理实体,基质金属蛋白酶-1 (matrix metalloproteinase-1,MMP-1)及组织型基质金属蛋白酶抑制因子-1(tissue inhibitor of matrix metalloproteinases-1,TIMP-1)共同表达在心肌成纤维母细胞,共同调节胶原代谢,一旦ECM的合成与降解平衡破坏,致使心肌纤维化。本实验通过检测持续性房颤组、阵发性房颤组及窦性心律组三组患者血清中心肌胶原代谢标志物及MMP-1、TIMP-1的表达水平,探讨心肌胶原代谢标志物与不同类型心房颤动的关系,并进一步探讨心肌纤维化对左房内径及左室射血分数的影响。
方法选择同期住院的119例患者,其中持续性心房颤动(Persistent atrial fibrilla- tion ,Pe-Af)患者49例,阵发性心房颤动(Paroxysmal atrial fibrillation ,Pa-Af)患者40例,窦性心律(Sinus rhythm, SR)患者30例,分别为Pe-Af组、Pa-Af组、SR组。酶联免疫吸附法测定患者血清中I型胶原羧基端前肽(C-terminal propeptide of collagen type-I ,CICP)、I型前胶原羧基端前肽(C-terminal propeptide of procollagen type I ,PICP)、I型前胶原氨基端前肽(N-terminal propeptide of procollagen type I,PINP)、III型前胶原氨基端肽(N-terminal type III collagen peptide, PIIINP)及基质金属蛋白酶-1(MMP-1)、组织型基质金属蛋白酶抑制因子-1(TIMP-1)的含量,电化学发光免疫法测定患者血清中I型胶原羧基末端交联肽(C-terminal telopeptide of collagen type-I ,ICTP)的表达水平。
结果与SR组比较,心房颤动患者血清中CICP、PICP、PIIINP浓度显著增高(P<0.01),且Pe-Af组高于Pa-Af组(P<0.01) ,而3组中PINP无明显差异(P=0.054);与SR组比较,心房颤动患者血清中TIMP-1、ICTP浓度有显著升高(P<0.01),其中与组Pa-Af比较,Pe-Af组MMP-1减低(P<0.01), TIMP-1升高(P<0.01),而ICTP升高不明显(P =0.128)。将CICP、PICP、PIIINP、TIMP-1血清水平分别与左心房(left atrium,LA)内径和左心室射血分数(left ventricular ejection fraction,LVEF)行相关性分析,结果显示CICP、PICP、PIIINP、TIMP-1血清水平与LA内径呈正相关,相关系数分别为r=0.636、r=0.776、r=0.932、r=0.620;与LVEF呈较弱负相关,相关系数分别为r=-0.530、r=-0.568、r=-0.459、r=-0.499。
结论(1)不同类型心房颤动患者血清中心肌胶原代谢标志物表达有差异,心肌纤维化可能参与了房颤的发生及维持;(2)MMP-1活化具有时间依赖性,在阵发性房颤组表达增加,但持续性房颤组较窦性心律组无差异;(3)CICP、PICP、PIIINP、TIMP-1血清水平与LA内径大小呈正相关,与LVEF呈线性负相关,表明:左房内径越大,心肌纤维化程度越重;心脏收缩功能越差,心肌纤维化程度越重。
Objective Electrical remodeling and structural remodeling has relation to the occurrence and maintenance mechanism of atrial fibrillation. Atrial structural remodeling to promote excitement for anisotropic conduction, making the coupling between the heterogeneity of myocardial cells to increase, shortening the wavelength of the non-directional block is conducive to the formation of reentrant mechanisms, thus contributing to the occurrence and maintenance of atrial fibrillation. Myocardial fibrosis is the main performance of atrial structural remodeling,and the pathologic entity of extracellular matrix remodeling. Collagen is the principal structural protein, and collagen types I and III are the most abundant in the ECM. MMP-1 and TIMP-1 are coexpressed in cardiac fibroblasts and are regulated to maintain the architecture of the ECM,once the balance of synthesis and degradation of ECM damage, resulting in myocardial fibrosis. To investigeted the correlation between circulating levels of myocardial collagen degradation or synthesis markers and the pattern of atrial fibrillation,by detecting serum myocardial collagen metabolism markers and MMP-1, TIMP-1 in Pe-Af group, Pa-Af group and SR group.
Methods Serum C-terminal propeptide of collagen type-I (CICP), C-terminal propep- tide of procollagen type I (PICP) ,N-terminal propeptide of procollagen type I (PINP), N-terminal type III collagen peptide(PIIINP), matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinases-1 were measured as markers of collagen synthesis and degradation by enzyme-linked immunoadsorbent assay, and C-terminal telopeptide of collagen type-I (ICTP) was assayed using Electrochemiluminescence,in 49 patients with Pe-Af,40 patients with Pa-Af,and 30 healthy control subjects in sinus rhythm.
Results CICP, PICP and PIIINP were significantly higher in atrial fibrillation patients than in sinus rhythm study group (P<0.01),and Pe-Af group was higher than Pa-Af group (P <0.01),but no differences were found in PINP levels between atrial fibrillation and sinus rhythm study groups(P=0.054). Atrial fibrillation group had significantly higher levels of TIMP-1 and ICTP(P <0.01) compared with sinus rhythm group.Pe-Af group had lower levels of MMP-1(P <0.01),but higher levels TIMP-1 (P<0.01), when compared with Pa-Af group, and levels of ICTP tended to be higher (P=0.128). In all Af patients taken together, there was a positive correlation between CICP,PICP,PIIINP, and TIMP levels and LA dimension,and the correlation coefficient r were 0.636 ,0.776,0.932,and 0.620 respectively. While there was a weak,inverse correlation between CICP,PICP,PIIINP,and TIMP levels and LVEF,and the correlation coefficient r were -0.530 ,-0.568,-0.459,and -0.499 respectively.
Conclusions Serum markers of myocardial collagen metabolism markers differed significantly between persistent atrial fibrillation and paroxysmal atrial fibrillation. Myocardial fibrosis is involved in the presence and maintenance of mechanisms of atrial fibrillation. MMP-1 activation in a time-dependent,which expression increased in the paroxysmal atrial fibrillation group.But no differences were found in MMP-1 levels between atrial fibrillation and sinus rhythm study groups. There was a positive correlation between CICP,PICP,PIIINP, and TIMP levels and LA dimension.While there was a weak,inverse correlation between CICP,PICP,PIIINP,and TIMP-1 levels and LVEF. The LA dimension larger,LVEF lower ,the more obvious of atrial fibrosis.
方法选择同期住院的119例患者,其中持续性心房颤动(Persistent atrial fibrilla- tion ,Pe-Af)患者49例,阵发性心房颤动(Paroxysmal atrial fibrillation ,Pa-Af)患者40例,窦性心律(Sinus rhythm, SR)患者30例,分别为Pe-Af组、Pa-Af组、SR组。酶联免疫吸附法测定患者血清中I型胶原羧基端前肽(C-terminal propeptide of collagen type-I ,CICP)、I型前胶原羧基端前肽(C-terminal propeptide of procollagen type I ,PICP)、I型前胶原氨基端前肽(N-terminal propeptide of procollagen type I,PINP)、III型前胶原氨基端肽(N-terminal type III collagen peptide, PIIINP)及基质金属蛋白酶-1(MMP-1)、组织型基质金属蛋白酶抑制因子-1(TIMP-1)的含量,电化学发光免疫法测定患者血清中I型胶原羧基末端交联肽(C-terminal telopeptide of collagen type-I ,ICTP)的表达水平。
结果与SR组比较,心房颤动患者血清中CICP、PICP、PIIINP浓度显著增高(P<0.01),且Pe-Af组高于Pa-Af组(P<0.01) ,而3组中PINP无明显差异(P=0.054);与SR组比较,心房颤动患者血清中TIMP-1、ICTP浓度有显著升高(P<0.01),其中与组Pa-Af比较,Pe-Af组MMP-1减低(P<0.01), TIMP-1升高(P<0.01),而ICTP升高不明显(P =0.128)。将CICP、PICP、PIIINP、TIMP-1血清水平分别与左心房(left atrium,LA)内径和左心室射血分数(left ventricular ejection fraction,LVEF)行相关性分析,结果显示CICP、PICP、PIIINP、TIMP-1血清水平与LA内径呈正相关,相关系数分别为r=0.636、r=0.776、r=0.932、r=0.620;与LVEF呈较弱负相关,相关系数分别为r=-0.530、r=-0.568、r=-0.459、r=-0.499。
结论(1)不同类型心房颤动患者血清中心肌胶原代谢标志物表达有差异,心肌纤维化可能参与了房颤的发生及维持;(2)MMP-1活化具有时间依赖性,在阵发性房颤组表达增加,但持续性房颤组较窦性心律组无差异;(3)CICP、PICP、PIIINP、TIMP-1血清水平与LA内径大小呈正相关,与LVEF呈线性负相关,表明:左房内径越大,心肌纤维化程度越重;心脏收缩功能越差,心肌纤维化程度越重。
Objective Electrical remodeling and structural remodeling has relation to the occurrence and maintenance mechanism of atrial fibrillation. Atrial structural remodeling to promote excitement for anisotropic conduction, making the coupling between the heterogeneity of myocardial cells to increase, shortening the wavelength of the non-directional block is conducive to the formation of reentrant mechanisms, thus contributing to the occurrence and maintenance of atrial fibrillation. Myocardial fibrosis is the main performance of atrial structural remodeling,and the pathologic entity of extracellular matrix remodeling. Collagen is the principal structural protein, and collagen types I and III are the most abundant in the ECM. MMP-1 and TIMP-1 are coexpressed in cardiac fibroblasts and are regulated to maintain the architecture of the ECM,once the balance of synthesis and degradation of ECM damage, resulting in myocardial fibrosis. To investigeted the correlation between circulating levels of myocardial collagen degradation or synthesis markers and the pattern of atrial fibrillation,by detecting serum myocardial collagen metabolism markers and MMP-1, TIMP-1 in Pe-Af group, Pa-Af group and SR group.
Methods Serum C-terminal propeptide of collagen type-I (CICP), C-terminal propep- tide of procollagen type I (PICP) ,N-terminal propeptide of procollagen type I (PINP), N-terminal type III collagen peptide(PIIINP), matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinases-1 were measured as markers of collagen synthesis and degradation by enzyme-linked immunoadsorbent assay, and C-terminal telopeptide of collagen type-I (ICTP) was assayed using Electrochemiluminescence,in 49 patients with Pe-Af,40 patients with Pa-Af,and 30 healthy control subjects in sinus rhythm.
Results CICP, PICP and PIIINP were significantly higher in atrial fibrillation patients than in sinus rhythm study group (P<0.01),and Pe-Af group was higher than Pa-Af group (P <0.01),but no differences were found in PINP levels between atrial fibrillation and sinus rhythm study groups(P=0.054). Atrial fibrillation group had significantly higher levels of TIMP-1 and ICTP(P <0.01) compared with sinus rhythm group.Pe-Af group had lower levels of MMP-1(P <0.01),but higher levels TIMP-1 (P<0.01), when compared with Pa-Af group, and levels of ICTP tended to be higher (P=0.128). In all Af patients taken together, there was a positive correlation between CICP,PICP,PIIINP, and TIMP levels and LA dimension,and the correlation coefficient r were 0.636 ,0.776,0.932,and 0.620 respectively. While there was a weak,inverse correlation between CICP,PICP,PIIINP,and TIMP levels and LVEF,and the correlation coefficient r were -0.530 ,-0.568,-0.459,and -0.499 respectively.
Conclusions Serum markers of myocardial collagen metabolism markers differed significantly between persistent atrial fibrillation and paroxysmal atrial fibrillation. Myocardial fibrosis is involved in the presence and maintenance of mechanisms of atrial fibrillation. MMP-1 activation in a time-dependent,which expression increased in the paroxysmal atrial fibrillation group.But no differences were found in MMP-1 levels between atrial fibrillation and sinus rhythm study groups. There was a positive correlation between CICP,PICP,PIIINP, and TIMP levels and LA dimension.While there was a weak,inverse correlation between CICP,PICP,PIIINP,and TIMP-1 levels and LVEF. The LA dimension larger,LVEF lower ,the more obvious of atrial fibrosis.
引文
1.周自强,胡大一,陈捷,等.中国心房颤动现状的流行病学研究[J].中华内科学杂志,2004,43:191-494.
2. Kourliouros A, Savelieva I, Kiotsekoglou A, et al.Current concepts in the pathogenesis of atrial fibrillation[J].Am Heart J,2009,157:243-52.
3.石桂良,潘闽,朱建华.心房颤动与炎症[J].国际心血管杂志.2008:2:84-87.
4.张运,徐瑞.心肌纤维化——心力衰竭治疗的新靶标[J].中华医学杂志,2006,86:1155—7.
5. D’Armiento J. Matrix metalloproteinase disruption of the extracellular matrix and cardiac dysfunction[J].Trends Cardiovasc Med,2002,12:97–101.
6. Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the manage ment of patients with atrial fibrillation: a report of the american college of cardiology/American heart association task force on practice guidelines and the european society of cardiology committee for practice guidelines (writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation):developed in collaboration with the European heart rhythm association and the heart rhythm society[J].Circulation,2006,114:e257-354.
7. Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for themanagement of patients with atrial fibrillation: full text: a report of the Americancollege of cardiology/American heart association task force on practice guidelines and the European society of cardiology committee for practice guidelines (writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation) developed in collaboration with the European heart rhythm association and the heart rhythm society[J].Europace,2006,8:651-745.
8. Kourliouros A, Savelieva I, Kiotsekoglou A, et al.Current concepts in the patho- genesis of atrial fibrillation[J].Am Heart J,2009,157:243-52.
9. Everett TH 4th,Olgin JE.Atrial fibrosis and the mechanisms of atfial fibrillation [J].Heart Rhythm,2007,4:S24-7.
10.邢晓倩,徐健.心肌纤维化与心房颤动的发生及维持[J].心血管病学进展,2009- 01-056.
11. Li D, Fareh S, Leung TK, et al.Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort[J].Circulation,1999,100:87-95.
12. Corradi D, Callegari S, Benussi S, et al. Regional left atrial interstitial remodeling in patients with chronic atrial fibrillation undergoing mitral-valve surgery [J].Virchows Arch, 2004,445:498-505.
13. Corradi D, Callegari S, Benussi S, et al. Myocyte changes and their left atrial distribution in patients with chronic atrial fibrillation related to mitral valve disease[J].Hum Pathol,2005 ,36:1080-9.
14. Zannad F, Rossignol P, Iraqi W. Extracellular matrix fibrotic markers in heart failure[J]. Heart Fail Rev,2010 ,15:319-29.
15.谭蓓,张海澄,曹磊等.老年心房颤动患者胶原代谢与基质金属蛋白酶表达的研究[J].中华老年医学杂志,2008,27:428-31.
16. Schwartzkopff B, Fassbach M, Pelzer B, et al. Elevated serum markers of collagen degradation in patients with mild to moderate dilated cardiomyopathy[J]. Eur J Heart Fail,2002,4:439-44.
17. Lopez B, Gonzalez A, Querejeta R,et al . The use of collagen-derived serum peptides for the clinical assessment of hypertensive heart disease[J].J Hypertens, 2005,23: 1445–1451.
18. Querejeta R, Varo N, Lopez B et al .Serum carboxyterminal propeptide of procollagen type I is a marker of myocardial fibrosis in hypertensive heart disease[J]. Circulation,2000,101:1729–1735.
19. Querejeta R, Lopez B, Gonzalez A et al . Increased collagen type I synthesis in patients with heart failure of hypertensive origin: relation to myocardial fibrosis[J]. Circulation, 2004,110:1263–1268.
20. Diez J, Querejeta R, Lopez B,et al . Losartan-dependent regression of myocardialfibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients[J].Circulation,2002,105:2512–2517.
21. Zannad F, Rossignol P, Iraqi W. Extracellular matrix fibrotic markers in heart failure[J]. Heart Fail Rev,2010 ,15:319-29.
22.汤宝鹏,甘天翊,许国荣,等.慢性心房颤动心房肌间质纤维化的分子机制研究[J].中华心律失常学杂志,2009,13:369–72.
23. Madrid AH, Marín IM, Cervantes CE, et al. Prevention of recurrences in patientswith lone atrial fibrillation. The dose-dependent effect of angiotensin II receptorblockers[J]. J Renin Angiotensin Aldosterone Syst,2004,5:114-20.
24. Boldt A, Scholl A, Garbade J,et al.ACE-inhibitor treatment attenuates atrial structural remodeling in patients with lone chronic atrial fibrillation[J]. Basic Res Cardiol,2006,101:261-7.
25. Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure,function, and biochemistry[J].Circ Res,2003,92: 827–39.
26. AnnéW, Willems R, Roskams T, Sergeant P, et al. Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation[J]. Cardiovasc Res,2005,67:655-66.
27. Chrysostomakis SI, Karalis IK, Simantirakis EN, et al. Angiotensin II type 1 receptor inhibition is associated with reduced tachyarrhythmia-induced ventricular interstitial fibrosis in a goat atrial fibrillation model[J].Cardiovasc Drugs Ther, 2007,21:357-65.
28. Chiu YT, Wu TJ, Wei HJ, et al. Increased extracellular collagen matrix in myocardial sleeves of pulmonary veins: an additional mechanism facilitating repetitive rapid activities in chronic pacing-induced sustained atrial fibrillation[J].J Cardiovasc Electrophysiol,2005,16:753-9.
29. Pappone C, Augello G, Sala S, et al. A Randomized Trial of Circumferential Pulmonary Vein Ablation Versus Antiarrhythmic Drug Therapy in ParoxysmalAtrial Fibrillation: The APAF Study[J].J Am Coll Cardiol,2006,48:2340-7.
30. Oral H, Pappone C, Chugh A, et al.Circumferential pulmonary-vein ablation for chronic atrial fibrillation[J].N Engl J Med,2006 2;354:934-41.
31.陆再英,钟南山,谢毅,等.内科学[M].人民卫生出版社.2008年第7版:159-228.
32. Kallergis EM, Manios EG, Kanoupakis EM, et al. Extracellular matrix alterations in patients with paroxysmal and persistent atrial fibrillation: biochemical assessment of collagen type-I turnover[J].J Am Coll Cardiol,2008,52:211-5.
1. Zannad F, Rossignol P, Iraqi W. Extracellular matrix fibrotic markers in heart failure[J]. Heart Fail Rev,2010,15:319-29.
2. Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure,function, and biochemistry[J].Circ Res,2003,92: 827–39.
3. Weber KT .Monitoring tissue repair and fibrosis from a distance[J]. Circulation, 1997,96:2488–2492.
4. Risteli J, Risteli L .Analysing connective tissue metabolites in human serum. Biochemical,physiological and methodological aspects[J].Journal of Hepatology, 1995,22:77–81.
5. Jensen LT, Horslev-Petersen K, Toft P et al . Serum aminoterminal type III procollagen peptide reflects repair after acute myocardial infarction [J]. Circulation, 1990,81:52–57.
6. Zannad F, Pitt B. Biomarkers of Extracellular MatrixTurnover[J]. Heart Fail Clin,2009,5:589-99.
7. Belluzzi F, Sernesi L, Centola M,et al. Role of ACE-inhibitors in preventing atrial fibrillation relapses in normotensive patients[J]. Recenti Prog Med,2009,100: 508-11.
8. Madrid AH, Bueno MG, Rebollo JM, et al. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study[J].Circulation, 2002,106:331-6.
9. Vermes E, Tardif JC, Bourassa MG, et al. Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction: insight from the Studies Of Left Ventricular Dysfunction (SOLVD) trials[J].Circulation,2003,107:2926-31.
10. Bhuriya R, Singh M, Sethi A, et al. Prevention of Recurrent Atrial Fibrillation With Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers: A Systematic Review and Meta-Analysis of Randomized Trials[J].J CardiovascPharmacol Ther.2011.[Epub ahead of print]
11. Healey JS, Baranchuk A, Crystal E, et al. Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis[J]. J Am Coll Cardiol.2005,45:1832-9.
12. Nakashima H, Kumagai K, Urata H, et al.Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation[J].Circulation,2000,101:2612-7.
13. Madrid AH, Bueno MG, Rebollo JM, et al. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study[J].Circulation,2002,106:331-6.
14. Wachtell K, Hornestam B, Lehto M, et al. Cardiovascular morbidity and mortality in hypertensive patients with a history of atrial fibrillation: The Losartan Intervention For End Point Reduction in Hypertension (LIFE) study[J]. J Am Coll Cardiol, 2005, 45:705-11.
15. Wachtell K, Lehto M, Gerdts E, et al. Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol: the Losartan Intervention For End Point Reduction in Hypertension (LIFE) study[J]. J Am Coll Cardiol,2005,45:712-9.
16.裴德安,李莉,徐志云,等.心房颤动患者心房肌盐皮质激素受体表达研究[J].中华心血管病,2007,35:114-8.
17.刘伟利,王桂芳.螺内酯联合胺碘酮治疗非瓣膜病阵发性房颤的临床研究[J].中国心血管病研究,2008,6:764-6.
18. Iraqi W, Rossignol P, Angioi M, et al. Extracellular cardiac matrix biomarkers in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study[J].Circulation, 2009, 119:2471-9.
19. Kuhn EW, Liakopoulos OJ, Borys MJ, et al. Statins improve surgical ablation outcomes for atrial fibrillation in patients undergoing concomitant cardiacurgery[J].Interact Cardiovasc Thorac Surg,2010,11:24-8.
20. Rahimi K, Emberson J, McGale P, et al. Effect of statins on atrial fibrillation: collaborative meta-analysis of published and unpublished evidence from randomised controlled trials[J]. BMJ,2011,16;342:d1250.
2. Kourliouros A, Savelieva I, Kiotsekoglou A, et al.Current concepts in the pathogenesis of atrial fibrillation[J].Am Heart J,2009,157:243-52.
3.石桂良,潘闽,朱建华.心房颤动与炎症[J].国际心血管杂志.2008:2:84-87.
4.张运,徐瑞.心肌纤维化——心力衰竭治疗的新靶标[J].中华医学杂志,2006,86:1155—7.
5. D’Armiento J. Matrix metalloproteinase disruption of the extracellular matrix and cardiac dysfunction[J].Trends Cardiovasc Med,2002,12:97–101.
6. Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the manage ment of patients with atrial fibrillation: a report of the american college of cardiology/American heart association task force on practice guidelines and the european society of cardiology committee for practice guidelines (writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation):developed in collaboration with the European heart rhythm association and the heart rhythm society[J].Circulation,2006,114:e257-354.
7. Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for themanagement of patients with atrial fibrillation: full text: a report of the Americancollege of cardiology/American heart association task force on practice guidelines and the European society of cardiology committee for practice guidelines (writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation) developed in collaboration with the European heart rhythm association and the heart rhythm society[J].Europace,2006,8:651-745.
8. Kourliouros A, Savelieva I, Kiotsekoglou A, et al.Current concepts in the patho- genesis of atrial fibrillation[J].Am Heart J,2009,157:243-52.
9. Everett TH 4th,Olgin JE.Atrial fibrosis and the mechanisms of atfial fibrillation [J].Heart Rhythm,2007,4:S24-7.
10.邢晓倩,徐健.心肌纤维化与心房颤动的发生及维持[J].心血管病学进展,2009- 01-056.
11. Li D, Fareh S, Leung TK, et al.Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort[J].Circulation,1999,100:87-95.
12. Corradi D, Callegari S, Benussi S, et al. Regional left atrial interstitial remodeling in patients with chronic atrial fibrillation undergoing mitral-valve surgery [J].Virchows Arch, 2004,445:498-505.
13. Corradi D, Callegari S, Benussi S, et al. Myocyte changes and their left atrial distribution in patients with chronic atrial fibrillation related to mitral valve disease[J].Hum Pathol,2005 ,36:1080-9.
14. Zannad F, Rossignol P, Iraqi W. Extracellular matrix fibrotic markers in heart failure[J]. Heart Fail Rev,2010 ,15:319-29.
15.谭蓓,张海澄,曹磊等.老年心房颤动患者胶原代谢与基质金属蛋白酶表达的研究[J].中华老年医学杂志,2008,27:428-31.
16. Schwartzkopff B, Fassbach M, Pelzer B, et al. Elevated serum markers of collagen degradation in patients with mild to moderate dilated cardiomyopathy[J]. Eur J Heart Fail,2002,4:439-44.
17. Lopez B, Gonzalez A, Querejeta R,et al . The use of collagen-derived serum peptides for the clinical assessment of hypertensive heart disease[J].J Hypertens, 2005,23: 1445–1451.
18. Querejeta R, Varo N, Lopez B et al .Serum carboxyterminal propeptide of procollagen type I is a marker of myocardial fibrosis in hypertensive heart disease[J]. Circulation,2000,101:1729–1735.
19. Querejeta R, Lopez B, Gonzalez A et al . Increased collagen type I synthesis in patients with heart failure of hypertensive origin: relation to myocardial fibrosis[J]. Circulation, 2004,110:1263–1268.
20. Diez J, Querejeta R, Lopez B,et al . Losartan-dependent regression of myocardialfibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients[J].Circulation,2002,105:2512–2517.
21. Zannad F, Rossignol P, Iraqi W. Extracellular matrix fibrotic markers in heart failure[J]. Heart Fail Rev,2010 ,15:319-29.
22.汤宝鹏,甘天翊,许国荣,等.慢性心房颤动心房肌间质纤维化的分子机制研究[J].中华心律失常学杂志,2009,13:369–72.
23. Madrid AH, Marín IM, Cervantes CE, et al. Prevention of recurrences in patientswith lone atrial fibrillation. The dose-dependent effect of angiotensin II receptorblockers[J]. J Renin Angiotensin Aldosterone Syst,2004,5:114-20.
24. Boldt A, Scholl A, Garbade J,et al.ACE-inhibitor treatment attenuates atrial structural remodeling in patients with lone chronic atrial fibrillation[J]. Basic Res Cardiol,2006,101:261-7.
25. Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure,function, and biochemistry[J].Circ Res,2003,92: 827–39.
26. AnnéW, Willems R, Roskams T, Sergeant P, et al. Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation[J]. Cardiovasc Res,2005,67:655-66.
27. Chrysostomakis SI, Karalis IK, Simantirakis EN, et al. Angiotensin II type 1 receptor inhibition is associated with reduced tachyarrhythmia-induced ventricular interstitial fibrosis in a goat atrial fibrillation model[J].Cardiovasc Drugs Ther, 2007,21:357-65.
28. Chiu YT, Wu TJ, Wei HJ, et al. Increased extracellular collagen matrix in myocardial sleeves of pulmonary veins: an additional mechanism facilitating repetitive rapid activities in chronic pacing-induced sustained atrial fibrillation[J].J Cardiovasc Electrophysiol,2005,16:753-9.
29. Pappone C, Augello G, Sala S, et al. A Randomized Trial of Circumferential Pulmonary Vein Ablation Versus Antiarrhythmic Drug Therapy in ParoxysmalAtrial Fibrillation: The APAF Study[J].J Am Coll Cardiol,2006,48:2340-7.
30. Oral H, Pappone C, Chugh A, et al.Circumferential pulmonary-vein ablation for chronic atrial fibrillation[J].N Engl J Med,2006 2;354:934-41.
31.陆再英,钟南山,谢毅,等.内科学[M].人民卫生出版社.2008年第7版:159-228.
32. Kallergis EM, Manios EG, Kanoupakis EM, et al. Extracellular matrix alterations in patients with paroxysmal and persistent atrial fibrillation: biochemical assessment of collagen type-I turnover[J].J Am Coll Cardiol,2008,52:211-5.
1. Zannad F, Rossignol P, Iraqi W. Extracellular matrix fibrotic markers in heart failure[J]. Heart Fail Rev,2010,15:319-29.
2. Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure,function, and biochemistry[J].Circ Res,2003,92: 827–39.
3. Weber KT .Monitoring tissue repair and fibrosis from a distance[J]. Circulation, 1997,96:2488–2492.
4. Risteli J, Risteli L .Analysing connective tissue metabolites in human serum. Biochemical,physiological and methodological aspects[J].Journal of Hepatology, 1995,22:77–81.
5. Jensen LT, Horslev-Petersen K, Toft P et al . Serum aminoterminal type III procollagen peptide reflects repair after acute myocardial infarction [J]. Circulation, 1990,81:52–57.
6. Zannad F, Pitt B. Biomarkers of Extracellular MatrixTurnover[J]. Heart Fail Clin,2009,5:589-99.
7. Belluzzi F, Sernesi L, Centola M,et al. Role of ACE-inhibitors in preventing atrial fibrillation relapses in normotensive patients[J]. Recenti Prog Med,2009,100: 508-11.
8. Madrid AH, Bueno MG, Rebollo JM, et al. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study[J].Circulation, 2002,106:331-6.
9. Vermes E, Tardif JC, Bourassa MG, et al. Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction: insight from the Studies Of Left Ventricular Dysfunction (SOLVD) trials[J].Circulation,2003,107:2926-31.
10. Bhuriya R, Singh M, Sethi A, et al. Prevention of Recurrent Atrial Fibrillation With Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers: A Systematic Review and Meta-Analysis of Randomized Trials[J].J CardiovascPharmacol Ther.2011.[Epub ahead of print]
11. Healey JS, Baranchuk A, Crystal E, et al. Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis[J]. J Am Coll Cardiol.2005,45:1832-9.
12. Nakashima H, Kumagai K, Urata H, et al.Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation[J].Circulation,2000,101:2612-7.
13. Madrid AH, Bueno MG, Rebollo JM, et al. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study[J].Circulation,2002,106:331-6.
14. Wachtell K, Hornestam B, Lehto M, et al. Cardiovascular morbidity and mortality in hypertensive patients with a history of atrial fibrillation: The Losartan Intervention For End Point Reduction in Hypertension (LIFE) study[J]. J Am Coll Cardiol, 2005, 45:705-11.
15. Wachtell K, Lehto M, Gerdts E, et al. Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol: the Losartan Intervention For End Point Reduction in Hypertension (LIFE) study[J]. J Am Coll Cardiol,2005,45:712-9.
16.裴德安,李莉,徐志云,等.心房颤动患者心房肌盐皮质激素受体表达研究[J].中华心血管病,2007,35:114-8.
17.刘伟利,王桂芳.螺内酯联合胺碘酮治疗非瓣膜病阵发性房颤的临床研究[J].中国心血管病研究,2008,6:764-6.
18. Iraqi W, Rossignol P, Angioi M, et al. Extracellular cardiac matrix biomarkers in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study[J].Circulation, 2009, 119:2471-9.
19. Kuhn EW, Liakopoulos OJ, Borys MJ, et al. Statins improve surgical ablation outcomes for atrial fibrillation in patients undergoing concomitant cardiacurgery[J].Interact Cardiovasc Thorac Surg,2010,11:24-8.
20. Rahimi K, Emberson J, McGale P, et al. Effect of statins on atrial fibrillation: collaborative meta-analysis of published and unpublished evidence from randomised controlled trials[J]. BMJ,2011,16;342:d1250.