膜联蛋白A5基因突变与中国人扩张型心肌病相关性研究
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摘要
目的：扩张型心肌病(Dilated Cardiomyopathy, DCM)是以一侧和/或两侧心腔扩大、心肌收缩功能障碍以及易出现各种心律失常为特征的原发性心肌疾病。该病缺乏有效的早期诊断和治疗手段,具有较高的病残率和较低的生存率。其发病原因尚不完全清楚,但大量的研究证实基因突变与DCM发病相关,这为我们探索DCM的发病、寻求基因诊断和治疗提供了依据。膜联蛋白家族(Annexins)已有13个成员,即Annexins A1～13,它们共同的特点是具有与Ca2+和脂类结合的特性。心脏中有丰富的Annexin A5,它对心肌细胞的Ca2+转运起调节作用。研究表明心肌细胞中的Annexin A5可能通过与Ca2+转运调节蛋白一起影响Ca2+转运进而影响Ca2+稳态,而心肌的收缩与舒张功能障碍与心肌细胞内Ca2+转运异常有关。但到目前为止,尚未见Annexin A5基因突变与DCM的相关研究报道。本课题旨在研究中国川南地区Annexin A5基因突变与DCM患者的相关性,探讨DCM患者的遗传学发病机制,为寻求基因诊断和治疗提供更多的依据。方法：本研究采取聚合酶链反应—变性高效液相色谱(Polymerase Chain Raction-Denaturing High Performance Liquid Chromatography, PCR-DHPLC)技术并结合核苷酸序列测定对153例DCM患者和141例健康对照者Annexin A5基因第2-13外显子进行检测与分析。结果：通过上述方法,在153例DCM患者中共发现Annexin A5基因突变位点3个,即：Annexin A5基因第403位点基因突变：C→T突变(C403T)；第430位点基因突变：C→G突变(C430G)；第434位点基因突变：T→A突变(T434A)。上述突变均为DCM组特有,对照组中未发现任何突变。上述突变未导致氨基酸性质的改变。结论：本研究首次发现Annexin A5基因第2外显子存在基因突变,并且可能使Annexin A5功能紊乱,从而推论该突变可能与中国川南地区DCM的发病相关。
objective:Dilated cardiomyopathy (DCM) is a primary myocardial disease characterized by left and/or right ventricular dialation and impaired contraction of myocardium.It has highly morbility and mortality for there was not effective means to early-diagnosis and cure.Although the cause of DCM is not clear,but it has beenreports that gene mutation are associated with DCM,which provides us more evidence to develop genetic diagnosis and early cure. Annexins are a family of 13 proteins known to bind phospholipids (PL) in a Ca2+-dependent way. The 13 Annexins named as Annexins A1-A13.Annexin A5 is one of the most abundant annexins in human myocardium. Annexin A5 may be able to interact with Ca2+ handling proteins involved in Ca2 +cycling and therefore play a role in Ca2+ homeostasis. A major mechanism of both systolic and diastolic dysfunction is thought to be abnormal intracellular Ca2+ handling. But we did nothing about Annexin A5 gene mutation(s) and DCM.To investigate the relationship between the Annexin A5 gene mutation(s) and DCM patients in South Sichuan,our research may provide a new path to explore the pathogenesis of DCM patients and more basis for gene diagnosis and gene therapy. Methods:The PCR-DHPLC(Polymerase Chain Raction-Denaturing High Performance Liquid Chromatography) and DNA sequencing analysis were used to detect the mutation of these exons(2-13) of Annexin A5 gene in 153 cases of DCM patients and 141 healthy controls. Results:Through this method,we fond 3 mutations in Annexin A5 gene in DCM patients.The change did not result in amino acid change.No mutation was identified in controls. Conclusion:It is for the first time we found 3 mutations in Annexin A5 gene in Chinese DCM patients.The mutations in Annexin A5 gene may be associated with DCM.
objective:Dilated cardiomyopathy (DCM) is a primary myocardial disease characterized by left and/or right ventricular dialation and impaired contraction of myocardium.It has highly morbility and mortality for there was not effective means to early-diagnosis and cure.Although the cause of DCM is not clear,but it has beenreports that gene mutation are associated with DCM,which provides us more evidence to develop genetic diagnosis and early cure. Annexins are a family of 13 proteins known to bind phospholipids (PL) in a Ca2+-dependent way. The 13 Annexins named as Annexins A1-A13.Annexin A5 is one of the most abundant annexins in human myocardium. Annexin A5 may be able to interact with Ca2+ handling proteins involved in Ca2 +cycling and therefore play a role in Ca2+ homeostasis. A major mechanism of both systolic and diastolic dysfunction is thought to be abnormal intracellular Ca2+ handling. But we did nothing about Annexin A5 gene mutation(s) and DCM.To investigate the relationship between the Annexin A5 gene mutation(s) and DCM patients in South Sichuan,our research may provide a new path to explore the pathogenesis of DCM patients and more basis for gene diagnosis and gene therapy. Methods:The PCR-DHPLC(Polymerase Chain Raction-Denaturing High Performance Liquid Chromatography) and DNA sequencing analysis were used to detect the mutation of these exons(2-13) of Annexin A5 gene in 153 cases of DCM patients and 141 healthy controls. Results:Through this method,we fond 3 mutations in Annexin A5 gene in DCM patients.The change did not result in amino acid change.No mutation was identified in controls. Conclusion:It is for the first time we found 3 mutations in Annexin A5 gene in Chinese DCM patients.The mutations in Annexin A5 gene may be associated with DCM.
引文
1. Felker GM, Thompson RE, Hare JM, et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy[J].N Engl J Med. Apr 13 2000;342(15):1077-1084.
2. Douglas P.Zips,Peter Libby,Rbert O.Bonow,et al.BRAUNWALD'S HEART DISEASE[M].Authorized English language reprint edtion published by the Proprietor.2005;981-259-472-478.
3. Codd MB, Sugrue DD, Gersh BJ, et a.Epidemiology of idiopathic dilated and hypertrophic cardiomyopathy.A population-based study in Olmsted County[J].Minnesota,1975-1984.Circulation,1989,80:564-572.
4.王志民,邹玉宝,宋雷,等。超声心动图检查调查8080例成人肥厚型心肌病患病率[J].中华心血管病杂志,2004,32：1090-1094.
5. Franz WM, Muller OJ, Katus HA. Cardiomyopathies:from genetics to the prospect of treatment[J]. Lancet. Nov 10 2001;358(9293):1627-1637.
6. Benevolensky D, Belikova Y, Mohammadzadeh R, et al. Expression and localization of the annexins Ⅱ, Ⅴ and Ⅵ in myocardium from patients with end-stage heart failure[J].Lab Invest 2000;80:123-133.
7. Bossuyt J, Taylor BE, James-Kracke M, et al. Evidence for cardiac sodium-calcium exchanger association with caveolin-3[J]. FEBS Lett 2002;511(1-3):113-117.
8. Camors E,Charue D,Trouve P,et al.Association of annexin A5 withNa+/Ca2+ exchanger and caveolin-3 in non-failing and failing human heart[J]. J Mol Cell Cardiol.2006 Jan;40(1):47-55.
9. Hoogendoorn B, Norton N, Kirov G, et al. Cheap, accurate and rapid allele frequency estimation of single nucleotide polymorphisms by primer extension and DHPLC in DNA pools[J].Hum Genet. Nov 2000;107(5):488-493.
10. Liu W, Smith DI, Rechtzigel KJ, et al. Denaturing high performance liquid chromatography (DHPLC) used in the detection of germline and somatic mutations[J]. Nucleic Acids Res. Mar 15 1998;26(6):1396-1400.
11. Gross E, Arnold N, Goette J, et al. A comparison of BRCA1 mutation analysis by direct sequencing, SSCP and DHPLC[J]. Hum Genet. Jul-Aug 1999;105(1-2):72-78.
12. Wolford JK, Blunt D, Ballecer C, et al. High-throughput SNP detection by using DNA pooling and denaturing high performance liquid chromatography(DHPLC) [J]. Hum Genet. Nov 2000;107(5):483-487.
13. Wolford JK, Blunt D, Ballecer C, et al. High-throughput SNP detection by using DNA pooling and denaturing high performance liquid chromatography(DHPLC) [J]. Hum Genet. Nov 2000;107(5):483-487.
14. Tian H, Liu DM, Xu B, et al. Analysis of sequence-tagged site in bcr and abl genes by DNA pooling and dHPLC[J]. Zhongguo Shi Yan Xue Ye Xue Za Zhi.Jun 2005;13(3):468-471.
15. Williams NM, Spurlock G, Norton N, et al. Mutation screening and LD mapping in the VCFS deleted region of chromosome 22q11 in schizophrenia using a novel DNA pooling approach[J]. Mol Psychiatry. 2002;7(10):1092-1100.
16. van Tintelen,Hofstra RM,Katerberg H, et al. High yield of LMNA mutations in patients with dilated cardiomyopathy and/or conduction disease referred to cardiogenetics outpatient clinics[J]. AmHeart J.2007 Dec; 154(6):1130-1129.
17. Martins E, Silva-Cardoso J, Alves C, et al. Familial dilated cardiomyopathy with troponinT K210del mutation. Rev Port Cardiol[J].2006;25:295-300.
18. Otten E,Lekanne Dit Deprez RH,Weiss MM, et al.. Recurrent and founder mutations in the Netherlands:mutation p.K217del in troponin T2, causing dilated cardiomyopathy[J].Neth Heart J.2010 Oct;18(10):478-485.
19. Taylor MR, Slavov D, Ku L, et al. Prevalence of desmin mutations in dilated cardiomyopathy[J]. Circulation.2007 Mar 13; 115(10):1244-1251.
20. Kaski JP, Burch M, Elliott PM. Mutations in the cardiac Troponin C gene are a cause of idiopathic dilated cardiomyopathy in childhood[J]. Cardiol Young.2007 Dec;17(6):675-677.
21. Raynal P, Pollard HB. Annexins:the problem of assessing the biological role for a gene family of multifunctional calcium- and phospholipid-binding proteins[J]. Biochim Biophys Acta 1994;1197:63-93.
22. Ursula R,Volker G. Annexins-unique membrane binding proteins with diverse functions[J].Journal of Cell Science,2004,117(13):2631-2639.
23. van Heerde W L, de Groot P G, Reutelingsper ger C P M. The complexity of the phospholipid binding protein Annexin V [J].Thromb Haemost,1995, 73:1722179.
24. Thierry D,Jean-Paul M,Dems F,et al.Annexin V inhibits protein kinase C activity via a m echanism of phospholipid sequestration[J].Biochem J,1998, 330(2):1277-1282.
25. Reviakine I,Bergsma-Schutter W,Mazeres-Dubut C,et al.Surface topograph of the p3 and p6 annexin V crystal forms determined by atomic force microscopy[J]. Struct Biol;2000,131:234-239.
26. Van Heerde WL,de Groot PG,Reutelingsperger CPM. The complexity of the phospholipid binding protein annexinV[J].Thromb Haemost,1995,73(2): 172-179.
27. Benevolensky D, Belikova Y, Mohammadzadeh R, et al. Expression and localization of the annexins Ⅱ, Ⅴ, and Ⅵ in myocardium from patients with end-stage heart failure.Lab Invest[J].2000;80:123-133.
28. Schlaepfer DD, Jones J, Haigler HT,1992. Inhibition of protein kinase C by annexin Ⅴ[J]. Biochemistry 31:1886-1891.
29. RavassaSravassa S,Garia-BolaoI,Zudaire A, et al.Cardiac resynchronization therapy-induced left ventricular reverse remodelling is associated with reduced plasma annexinA5[J]. Cardiovasc Res.2010 Nov 1;88(2):304-13.
30. Pelouch V. Molecular aspects of regulation of cardiac contraction[J].Physiol Res,1995,44(1):53.
31.Mylotte K M, Cody V, Davis P, et al. Milrinone and thyroid hormone stimulate myocardial membrane Ca2+-ATPase activity and share structural homologies[J]. Proc Natl Acad Sci USA,1985,82(23):7974.
32. Cohn RD, Durbeej M,Moore SA, et al. Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sareospan complex [J].J Clin Invest,2001,107:Rl-R7.
33. Sleeper MM, Bish LT, Sweeney HL. Status of therapeutic gene transfer to treat canine dilated cardiomyopathy in dogs[J]. Vet Clin North Am Small Anim Pract.2010 Jul;40(4):717-724.
1. Raynal P, Pollard HB. Annexins:the problem of assessing thebiological role for a gene family of multifunctional calcium-and phospholipid-binding proteins[J].Biochim Biophys Acta.1994;1197:63-93.
2. Trouve P, Legot S, Belikova I, et al.Localization and quantitation of cardiac annexins Ⅱ, Ⅴ, and Ⅵ in hypertensive guinea pigs[J]. Am J Physiol.1999; 276:H1159-66.
3. Kim J, Hajjar KA. AnnexinⅡ:a plasminogen-plasminogen activator co-recepptor [J]. Front Biosci,2002,7:D341-D348.
4. Hajjar KA, Acharya SS, et al.AnnexinⅡ and regulation of cell surface fibrinolysis [J].Ann, N, Y. Acad, Sci.2000,902:265-271.
5. Benevolensky D, Belikova Y, Mohammadzadeh R, et al. Expression and localization of the annexins Ⅱ, Ⅴ and Ⅵ in myocardium from patients with end-stage heart failure[J].Lab Invest.2000;80:123-33.
6. Trouve'P, Legot S, Belikova I, et al(1999).Localization and quantification of cardiac annexins Ⅱ,ⅤandⅥ in hypertensive guinea pigs[J]. Am J Physiol. 276:H1159-H1166. (51.7±8)
7. Jans SW, de Jong YF, Reutelingsperger CP, et al(1998).Differential expression and localization of annexin Ⅴ in cardiac myocytes during growth and hypertrophy[J]. Mol Cell Biochem.178:229-236.
8. Doubell AF, Baster AJ, Thibault G, et al(1991). Annexin Ⅴ and Ⅵ:major calcium-dependent atrial secretory granule-bindingproteins[J].Hypertension. 18:648-656.
9. Schlaepfer DD, Jones J, Haigler HT,1992. Inhibition of protein kinase C by annexin V[J]. Biochemistry.31:1886-1891.
10. Bossuyt J, Taylor BE, James-Kracke M, et al. Evidence for cardiac sodium-calcium exchanger association with caveolin-3[J].FEBS Lett.2002; 511 (1-3):113-7.
11.Camors E, Charue D, Trouve P, et al. Association of annexin A5 with Na+/Ca2+ exchanger and caveolin-3 in non-failing and failing human heart[J]. J Mol Cell Cardiol.2006 Jan;40(1):47-55.
12. Zeglen S, Zakliczynski M, Nozynski J, et al.sCD30,interleukin-1beta-converting enzyme and anti-Annexin V autoantibodies concentrations in heart transplant recipients[J].Transpl Immunol.2006 Nov;16(3-4):227-31.
13. Frostegard AG, Su J, von Landenberg P, et al. Effects of anti-cardiolipin antibodies and IVIg on annexin A5 binding to endothelial cells:implications for cardiovascular disease[J]. Scand J Rheumatol.2010;39(1):77-83.
14. Kietselaer BL, Reutelingsperger CP, Boersma HH, et al. Noninvasive detection of programmed cell loss with 99mTc-labeled annexin A5 in heart failure[J]. J Nucl Med.2007 Apr;48(4):562-7.
15. Ravassa S, Gonzalez A, Lopez B,et al. Upregulation of myocardial Annexir A5 in hypertensive heart disease:association with systolic dysfunction[J] Eur Heart J.2007 Nov;28(22):2785-91.
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2. Douglas P.Zips,Peter Libby,Rbert O.Bonow,et al.BRAUNWALD'S HEART DISEASE[M].Authorized English language reprint edtion published by the Proprietor.2005;981-259-472-478.
3. Codd MB, Sugrue DD, Gersh BJ, et a.Epidemiology of idiopathic dilated and hypertrophic cardiomyopathy.A population-based study in Olmsted County[J].Minnesota,1975-1984.Circulation,1989,80:564-572.
4.王志民,邹玉宝,宋雷,等。超声心动图检查调查8080例成人肥厚型心肌病患病率[J].中华心血管病杂志,2004,32：1090-1094.
5. Franz WM, Muller OJ, Katus HA. Cardiomyopathies:from genetics to the prospect of treatment[J]. Lancet. Nov 10 2001;358(9293):1627-1637.
6. Benevolensky D, Belikova Y, Mohammadzadeh R, et al. Expression and localization of the annexins Ⅱ, Ⅴ and Ⅵ in myocardium from patients with end-stage heart failure[J].Lab Invest 2000;80:123-133.
7. Bossuyt J, Taylor BE, James-Kracke M, et al. Evidence for cardiac sodium-calcium exchanger association with caveolin-3[J]. FEBS Lett 2002;511(1-3):113-117.
8. Camors E,Charue D,Trouve P,et al.Association of annexin A5 withNa+/Ca2+ exchanger and caveolin-3 in non-failing and failing human heart[J]. J Mol Cell Cardiol.2006 Jan;40(1):47-55.
9. Hoogendoorn B, Norton N, Kirov G, et al. Cheap, accurate and rapid allele frequency estimation of single nucleotide polymorphisms by primer extension and DHPLC in DNA pools[J].Hum Genet. Nov 2000;107(5):488-493.
10. Liu W, Smith DI, Rechtzigel KJ, et al. Denaturing high performance liquid chromatography (DHPLC) used in the detection of germline and somatic mutations[J]. Nucleic Acids Res. Mar 15 1998;26(6):1396-1400.
11. Gross E, Arnold N, Goette J, et al. A comparison of BRCA1 mutation analysis by direct sequencing, SSCP and DHPLC[J]. Hum Genet. Jul-Aug 1999;105(1-2):72-78.
12. Wolford JK, Blunt D, Ballecer C, et al. High-throughput SNP detection by using DNA pooling and denaturing high performance liquid chromatography(DHPLC) [J]. Hum Genet. Nov 2000;107(5):483-487.
13. Wolford JK, Blunt D, Ballecer C, et al. High-throughput SNP detection by using DNA pooling and denaturing high performance liquid chromatography(DHPLC) [J]. Hum Genet. Nov 2000;107(5):483-487.
14. Tian H, Liu DM, Xu B, et al. Analysis of sequence-tagged site in bcr and abl genes by DNA pooling and dHPLC[J]. Zhongguo Shi Yan Xue Ye Xue Za Zhi.Jun 2005;13(3):468-471.
15. Williams NM, Spurlock G, Norton N, et al. Mutation screening and LD mapping in the VCFS deleted region of chromosome 22q11 in schizophrenia using a novel DNA pooling approach[J]. Mol Psychiatry. 2002;7(10):1092-1100.
16. van Tintelen,Hofstra RM,Katerberg H, et al. High yield of LMNA mutations in patients with dilated cardiomyopathy and/or conduction disease referred to cardiogenetics outpatient clinics[J]. AmHeart J.2007 Dec; 154(6):1130-1129.
17. Martins E, Silva-Cardoso J, Alves C, et al. Familial dilated cardiomyopathy with troponinT K210del mutation. Rev Port Cardiol[J].2006;25:295-300.
18. Otten E,Lekanne Dit Deprez RH,Weiss MM, et al.. Recurrent and founder mutations in the Netherlands:mutation p.K217del in troponin T2, causing dilated cardiomyopathy[J].Neth Heart J.2010 Oct;18(10):478-485.
19. Taylor MR, Slavov D, Ku L, et al. Prevalence of desmin mutations in dilated cardiomyopathy[J]. Circulation.2007 Mar 13; 115(10):1244-1251.
20. Kaski JP, Burch M, Elliott PM. Mutations in the cardiac Troponin C gene are a cause of idiopathic dilated cardiomyopathy in childhood[J]. Cardiol Young.2007 Dec;17(6):675-677.
21. Raynal P, Pollard HB. Annexins:the problem of assessing the biological role for a gene family of multifunctional calcium- and phospholipid-binding proteins[J]. Biochim Biophys Acta 1994;1197:63-93.
22. Ursula R,Volker G. Annexins-unique membrane binding proteins with diverse functions[J].Journal of Cell Science,2004,117(13):2631-2639.
23. van Heerde W L, de Groot P G, Reutelingsper ger C P M. The complexity of the phospholipid binding protein Annexin V [J].Thromb Haemost,1995, 73:1722179.
24. Thierry D,Jean-Paul M,Dems F,et al.Annexin V inhibits protein kinase C activity via a m echanism of phospholipid sequestration[J].Biochem J,1998, 330(2):1277-1282.
25. Reviakine I,Bergsma-Schutter W,Mazeres-Dubut C,et al.Surface topograph of the p3 and p6 annexin V crystal forms determined by atomic force microscopy[J]. Struct Biol;2000,131:234-239.
26. Van Heerde WL,de Groot PG,Reutelingsperger CPM. The complexity of the phospholipid binding protein annexinV[J].Thromb Haemost,1995,73(2): 172-179.
27. Benevolensky D, Belikova Y, Mohammadzadeh R, et al. Expression and localization of the annexins Ⅱ, Ⅴ, and Ⅵ in myocardium from patients with end-stage heart failure.Lab Invest[J].2000;80:123-133.
28. Schlaepfer DD, Jones J, Haigler HT,1992. Inhibition of protein kinase C by annexin Ⅴ[J]. Biochemistry 31:1886-1891.
29. RavassaSravassa S,Garia-BolaoI,Zudaire A, et al.Cardiac resynchronization therapy-induced left ventricular reverse remodelling is associated with reduced plasma annexinA5[J]. Cardiovasc Res.2010 Nov 1;88(2):304-13.
30. Pelouch V. Molecular aspects of regulation of cardiac contraction[J].Physiol Res,1995,44(1):53.
31.Mylotte K M, Cody V, Davis P, et al. Milrinone and thyroid hormone stimulate myocardial membrane Ca2+-ATPase activity and share structural homologies[J]. Proc Natl Acad Sci USA,1985,82(23):7974.
32. Cohn RD, Durbeej M,Moore SA, et al. Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sareospan complex [J].J Clin Invest,2001,107:Rl-R7.
33. Sleeper MM, Bish LT, Sweeney HL. Status of therapeutic gene transfer to treat canine dilated cardiomyopathy in dogs[J]. Vet Clin North Am Small Anim Pract.2010 Jul;40(4):717-724.
1. Raynal P, Pollard HB. Annexins:the problem of assessing thebiological role for a gene family of multifunctional calcium-and phospholipid-binding proteins[J].Biochim Biophys Acta.1994;1197:63-93.
2. Trouve P, Legot S, Belikova I, et al.Localization and quantitation of cardiac annexins Ⅱ, Ⅴ, and Ⅵ in hypertensive guinea pigs[J]. Am J Physiol.1999; 276:H1159-66.
3. Kim J, Hajjar KA. AnnexinⅡ:a plasminogen-plasminogen activator co-recepptor [J]. Front Biosci,2002,7:D341-D348.
4. Hajjar KA, Acharya SS, et al.AnnexinⅡ and regulation of cell surface fibrinolysis [J].Ann, N, Y. Acad, Sci.2000,902:265-271.
5. Benevolensky D, Belikova Y, Mohammadzadeh R, et al. Expression and localization of the annexins Ⅱ, Ⅴ and Ⅵ in myocardium from patients with end-stage heart failure[J].Lab Invest.2000;80:123-33.
6. Trouve'P, Legot S, Belikova I, et al(1999).Localization and quantification of cardiac annexins Ⅱ,ⅤandⅥ in hypertensive guinea pigs[J]. Am J Physiol. 276:H1159-H1166. (51.7±8)
7. Jans SW, de Jong YF, Reutelingsperger CP, et al(1998).Differential expression and localization of annexin Ⅴ in cardiac myocytes during growth and hypertrophy[J]. Mol Cell Biochem.178:229-236.
8. Doubell AF, Baster AJ, Thibault G, et al(1991). Annexin Ⅴ and Ⅵ:major calcium-dependent atrial secretory granule-bindingproteins[J].Hypertension. 18:648-656.
9. Schlaepfer DD, Jones J, Haigler HT,1992. Inhibition of protein kinase C by annexin V[J]. Biochemistry.31:1886-1891.
10. Bossuyt J, Taylor BE, James-Kracke M, et al. Evidence for cardiac sodium-calcium exchanger association with caveolin-3[J].FEBS Lett.2002; 511 (1-3):113-7.
11.Camors E, Charue D, Trouve P, et al. Association of annexin A5 with Na+/Ca2+ exchanger and caveolin-3 in non-failing and failing human heart[J]. J Mol Cell Cardiol.2006 Jan;40(1):47-55.
12. Zeglen S, Zakliczynski M, Nozynski J, et al.sCD30,interleukin-1beta-converting enzyme and anti-Annexin V autoantibodies concentrations in heart transplant recipients[J].Transpl Immunol.2006 Nov;16(3-4):227-31.
13. Frostegard AG, Su J, von Landenberg P, et al. Effects of anti-cardiolipin antibodies and IVIg on annexin A5 binding to endothelial cells:implications for cardiovascular disease[J]. Scand J Rheumatol.2010;39(1):77-83.
14. Kietselaer BL, Reutelingsperger CP, Boersma HH, et al. Noninvasive detection of programmed cell loss with 99mTc-labeled annexin A5 in heart failure[J]. J Nucl Med.2007 Apr;48(4):562-7.
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