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01-09-2013 | Original Contribution

Deficiency of cartilage oligomeric matrix protein causes dilated cardiomyopathy

Authors: Yaqian Huang, Jiahong Xia, Jingang Zheng, Bin Geng, Peng Liu, Fang Yu, Bo Liu, Hongquan Zhang, Mingjiang Xu, Ping Ye, Yi Zhu, Qingbo Xu, Xian Wang, Wei Kong

Published in: Basic Research in Cardiology | Issue 5/2013

Abstract

Alterations in cardiac extracellular matrix are involved in dilated cardiomyopathy (DCM) and its progression to heart failure. The matricellular protein cartilage oligomeric matrix protein (COMP) has been indicated localized in the heart. However, the role of COMP in cardiac homeostasis and disease remains elusive. COMP ^−/− mice, both male and female, developed DCM spontaneously at young age (3–5 months), with impaired cardiac function. Assessment of postnatal COMP ^−/− heart at 1 month, although functionally normal, revealed severe cardiac ultrastructure defect, in parallel with cardiomyocyte apoptosis, myofilament loss, connexin-43 deficiency and matrix metalloproteinase activation. Decreased COMP expression was observed in the heart sample of DCM patients compared with donor heart. Mechanistically, COMP ^−/− heart exhibited reduced integrin β1 expression and signaling. Ectopic expression of COMP or integrin β1 rescued COMP-deficiency-induced cardiomyocyte apoptosis, myofilament dissolution, and connexin-43 aberrance. Additionally, COMP directly bonded to the extracellular β-tail domain of integrin β1, prevented integrin β1 ubiquitination/degradation, and maintained the cardiac homeostasis. COMP-integrin β1 axis is a potential target of DCM.

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Apple FS, Jesse RL, Newby LK, Wu AH, Christenson RH (2007) National academy of clinical biochemistry and IFCC committee for standardization of markers of cardiac damage laboratory medicine practice guidelines: analytical issues for biochemical markers of acute coronary syndromes. Circulation 115:e352–e355. doi:10.1161/CIRCULATIONAHA.107.182881 PubMedCrossRef

Baudoin C, Goumans MJ, Mummery C, Sonnenberg A (1998) Knockout and knock-in of the β1 exon D define distinct roles for integrin splice variants in heart function and embryonic development. Gen Dev 12:1202–1216. doi:10.1101/gad.12.8.1202 CrossRef

Bell D, Campbell M, Wang X, Earle JA, Cosby SL, McDermott BJ (2006) Adrenomedullin gene delivery is cardio-protective in a model of chronic nitric oxide deficiency combining pressure overload, oxidative stress and cardiomyocyte hypertrophy. Cell Physiol Biochem 26:383–394. doi:10.1159/000320562 CrossRef

Bell D, Campbell M, Wang X, Earle JA, Cosby SL, McDermott BJ (2010) Adrenomedullin gene delivery is cardio-protective in a model of chronic nitric oxide deficiency combining pressure overload, oxidative stress and cardiomyocyte hypertrophy. Cell Physiol Biochem 26:383–394. doi:10.1159/000320562 PubMedCrossRef

Brancaccio M, Fratta L, Notte A, Hirsch E, Poulet R, Guazzone S, De Acetis M, Vecchione C, Marino G, Altruda F, Silengo L, Tarone G, Lembo G (2003) Melusin, a muscle-specific integrin β1-interacting protein, is required to prevent cardiac failure in response to chronic pressure overload. Nat Med 9:68–75. doi:10.1038/nm805 PubMedCrossRef

Bridgewater RE, Norman JC, Caswell PT (2012) Integrin trafficking at a glance. J Cell Sci 125:3695–3701. doi:10.1242/jcs.095810 PubMedCrossRef

Briggs MD, Hoffman SM, King LM, Olsen AS, Mohrenweiser H, Leroy JG, Mortier GR, Rimoin DL, Lachman RS, Gaines ES et al (1995) Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene. Nat Gen 10:330–336. doi:10.1038/ng0795-330 CrossRef

Darom A, Bening-Abu-Shach U, Broday L (2010) RNF-121 is an endoplasmic reticulum-membrane E3 ubiquitin ligase involved in the regulation of beta-integrin. Mol Biol Cell 21:1788–1798. doi:10.1091/mbc.E09-09-0774 PubMedCrossRef

Fang C, Carlson CS, Leslie MP, Tulli H, Stolerman E, Perris R, Ni L, Di Cesare PE (2000) Molecular cloning, sequencing, and tissue and developmental expression of mouse cartilage oligomeric matrix protein (COMP). J Orthop Res 18:593–603. doi:10.1002/jor.1100180412 PubMedCrossRef

10.

Foster CR, Singh M, Subramanian V, Singh K (2011) Ataxia telangiectasia mutated kinase plays a protective role in β-adrenergic receptor-stimulated cardiac myocyte apoptosis and myocardial remodeling. Mol Cell Biochem 353:13–22. doi:10.1007/s11010-011-0769-6 PubMedCrossRef

11.

Frangogiannis NG (2012) Matricellular proteins in cardiac adaptation and disease. Physiol Rev 92:635–688. doi:10.1152/physrev.00008.2011 PubMedCrossRef

12.

Frangogiannis NG, Ren G, Dewald O, Zymek P, Haudek S, Koerting A, Winkelmann K, Michael LH, Lawler J, Entman ML (2005) Critical role of endogenous thrombospondin-1 in preventing expansion of healing myocardial infarcts. Circulation 111:2935–2942. doi:10.1161/CIRCULATIONAHA.104.510354 PubMedCrossRef

13.

Gardin JM, Siri FM, Kitsis RN, Edwards JG, Leinwand LA (1995) Echocardiographic assessment of left ventricular mass and systolic function in mice. Circ Res 76:907–914. doi:10.1161/01.RES.76.5.907 PubMedCrossRef

14.

Gupta V, Gylling A, Alonso JL, Sugimori T, Ianakiev P, Xiong JP, Arnaout MA (2007) The beta-tail domain (betaTD) regulates physiologic ligand binding to integrin CD11b/CD18. Blood 109:3513–3520. doi:10.1182/blood-2005-11-056689 PubMedCrossRef

15.

Ieda M, Tsuchihashi T, Ivey KN, Ross RS, Hong TT, Shaw RM, Srivastava D (2009) Cardiac fibroblasts regulate myocardial proliferation through β1 integrin signaling. Dev Cell 16:233–244. doi:10.1016/j.devcel.2008.12.007 PubMedCrossRef

16.

Jannuzi AL, Bunch TA, West RF, Brower DL (2004) Identification of integrin beta subunit mutations that alter heterodimer function in situ. Mol Biol Cell 15:3829–3840. doi:10.1091/mbc.E04-02-0085 PubMedCrossRef

17.

Kaabeche K, Guenou H, Bouvard D, Didelot N, Listrat A, Marie PJ (2005) Cbl-mediated ubiquitination of α5 integrin subunit mediates fibronectin-dependent osteoblast detachment and apoptosis induced by FGFR2 activation. J Cell Sci 118:1223–1232. doi:10.1242/jcs.01679 PubMedCrossRef

18.

Krishnamurthy P, Subramanian V, Singh M, Singh K (2006) Deficiency of β1 integrins results in increased myocardial dysfunction after myocardial infarction. Heart 92:1309–1315. doi:10.1136/hrt.2005.071001 PubMedCrossRef

19.

Liang X, Sun Y, Ye M, Scimia MC, Cheng H, Martin J, Wang G, Rearden A, Wu C, Peterson KL, Powell HC, Evans SM, Chen J (2009) Targeted ablation of PINCH1 and PINCH2 from murine myocardium results in dilated cardiomyopathy and early postnatal lethality. Circulation 120:568–576. doi:10.1161/CIRCULATIONAHA.109.864686 PubMedCrossRef

20.

Lobert VH, Stenmark H (2010) Ubiquitination of alpha-integrin cytoplasmic tails. Comm Integr Biol 3:583–585. doi:10.4161/cib.3.6.13176 CrossRef

21.

Louch WE, Sheehan KA, Wolska BM (2011) Methods in cardiomyocyte isolation, culture, and gene transfer. J Mol Cell Cardiol 51:288–298. doi:10.1016/j.yjmcc.2011.06.012 PubMedCrossRef

22.

Luk A, Ahn E, Soor GS, Butany J (2009) Dilated cardiomyopathy: a review. J Clin Pathol 62:219–225. doi:10.1136/jcp.2008.060731 PubMedCrossRef

23.

Luo BH, Springer TA (2006) Integrin structures and conformational signaling. Curr Opin Cell Biol 18:579–586. doi:10.1016/j.ceb.2006.08.005 PubMedCrossRef

24.

Lynch JM, Maillet M, Vanhoutte D, Schloemer A, Sargent MA, Blair NS, Lynch KA, Okada T, Aronow BJ, Osinska H, Prywes R, Lorenz JN, Mori K, Lawler J, Robbins J, Molkentin JD (2012) A thrombospondin-dependent pathway for a protective ER stress response. Cell 149:1257–1268. doi:10.1016/j.cell.2012.03.050 PubMedCrossRef

25.

Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, Moss AJ, Seidman CE, Young JB (2006) Contemporary definitions and classification of the cardiomyopathies: an American heart association scientific statement from the council on clinical cardiology, heart failure and transplantation committee; quality of care and outcomes research and functional genomics and translational biology interdisciplinary working groups; and council on epidemiology and prevention. Circulation 113:1807–1816. doi:10.1161/CIRCULATIONAHA.106.174287 PubMedCrossRef

26.

Michels VV, Moll PP, Miller FA, Tajik AJ, Chu JS, Driscoll DJ, Burnett JC, Rodeheffer RJ, Chesebro JH, Tazelaar HD (1992) The frequency of familial dilated cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy. N Engl J Med 326:77–82. doi:10.1056/NEJM199201093260201 PubMedCrossRef

27.

Moore JR, Leinwand L, Warshaw DM (2012) Understanding cardiomyopathy phenotypes based on the functional impact of mutations in the myosin motor. Circ Res 111:375–385. doi:10.1161/CIRCRESAHA.110.223842 PubMedCrossRef

28.

Mould AP, McLeish JA, Huxley-Jones J, Goonesinghe AC, Hurlstone AF, Boot-Handford RP, Humphries MJ (2006) Identification of multiple integrin beta1 homologs in zebrafish (Danio rerio). BMC Cell Biol 7:24. doi:10.1186/1471-2121-7-24 PubMedCrossRef

29.

Peng X, Kraus MS, Wei H, Shen TL, Pariaut R, Alcaraz A, Ji G, Cheng L, Yang Q, Kotlikoff MI, Chen J, Chien K, Gu H, Guan JL (2006) Inactivation of focal adhesion kinase in cardiomyocytes promotes eccentric cardiac hypertrophy and fibrosis in mice. J Clin Inv 116:217–227. doi:10.1172/JCI24497 CrossRef

30.

Peng X, Wu X, Druso JE, Wei H, Park AY, Kraus MS, Alcaraz A, Chen J, Chien S, Cerione RA, Guan JL (2008) Cardiac developmental defects and eccentric right ventricular hypertrophy in cardiomyocyte focal adhesion kinase (FAK) conditional knockout mice. Proc Natl Acad Sci U S A 105:6638–6643. doi:10.1073/pnas.0802319105 PubMedCrossRef

31.

Piran S, Liu P, Morales A, Hershberger RE (2012) Where genome meets phenome: rationale for integrating genetic and protein biomarkers in the diagnosis and management of dilated cardiomyopathy and heart failure. J Am Coll Cardiol 60:283–289. doi:10.1016/j.jacc.2012.05.005 PubMedCrossRef

32.

Roura S, Bayes-Genis A (2009) Vascular dysfunction in idiopathic dilated cardiomyopathy. Nat Rev Cardiol 6:590–598. doi:10.1038/nrcardio.2009.130 PubMedCrossRef

33.

Schaefer A, Nethe M, Hordijk PL (2012) Ubiquitin links to cytoskeletal dynamics, cell adhesion and migration. Biochem J 442:13–25. doi:10.1042/BJ20111815 PubMedCrossRef

34.

Schlossarek S, Englmann DR, Sultan KR, Sauer M, Eschenhagen T, Carrier L (2012) Defective proteolytic systems in Mybpc3-targeted mice with cardiac hypertrophy. Bas Res Cardiol 107:235. doi:10.1007/s00395-011-0235-3 CrossRef

35.

Schonberger J, Seidman CE (2001) Many roads lead to a broken heart: the genetics of dilated cardiomyopathy. Am J Hum Gen 69:249–260. doi:10.1086/321978 CrossRef

36.

Schroen B, Heymans S, Sharma U, Blankesteijn WM, Pokharel S, Cleutjens JP, Porter JG, Evelo CT, Duisters R, van Leeuwen RE, Janssen BJ, Debets JJ, Smits JF, Daemen MJ, Crijns HJ, Bornstein P, Pinto YM (2004) Thrombospondin-2 is essential for myocardial matrix integrity: increased expression identifies failure-prone cardiac hypertrophy. Circ Res 95:515–522. doi:10.1161/01.RES.0000141019.20332.3e PubMedCrossRef

37.

Shai SY, Harpf AE, Babbitt CJ, Jordan MC, Fishbein MC, Chen J, Omura M, Leil TA, Becker KD, Jiang M, Smith DJ, Cherry SR, Loftus JC, Ross RS (2002) Cardiac myocyte-specific excision of the β1 integrin gene results in myocardial fibrosis and cardiac failure. Circ Res 90:458–464. doi:10.1161/hh0402.105790 PubMedCrossRef

38.

Sojak V, Mazic U, Cesen M, Schrader J, Danojevic N (2008) Cardiac resynchronization therapy for the failing Fontan patient. Ann Thorac Surg 85:2136–2138. doi:10.1016/j.athoracsur.2007.12.010 PubMedCrossRef

39.

Spinale FG (2002) Matrix metalloproteinases: regulation and dysregulation in the failing heart. Circ Res 90:520–530. doi:10.1161/01.RES.0000013290.12884.A3 PubMedCrossRef

40.

Spinale FG (2007) Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev 87:1285–1342. doi:10.1152/physrev.00012.2007 PubMedCrossRef

41.

Stenina OI, Topol EJ, Plow EF (2007) Thrombospondins, their polymorphisms, and cardiovascular disease. Arterioscler Thromb Vasc Biol 27:1886–1894. doi:10.1161/ATVBAHA.107.141713 PubMedCrossRef

42.

Svensson L, Aszodi A, Heinegard D, Hunziker EB, Reinholt FP, Fassler R, Oldberg A (2002) Cartilage oligomeric matrix protein-deficient mice have normal skeletal development. Mol Cell Biol 22:4366–4371. doi:10.1128/MCB.22.12.4366-4371.2002 PubMedCrossRef

43.

Swinnen M, Vanhoutte D, Van Almen GC, Hamdani N, Schellings MW, D’Hooge J, Van der Velden J, Weaver MS, Sage EH, Bornstein P, Verheyen FK, VandenDriessche T, Chuah MK, Westermann D, Paulus WJ, Van de Werf F, Schroen B, Carmeliet P, Pinto YM, Heymans S (2009) Absence of thrombospondin-2 causes age-related dilated cardiomyopathy. Circulation 120:1585–1597. doi:10.1161/CIRCULATIONAHA.109.863266 PubMedCrossRef

44.

Syed F, Diwan A, Hahn HS (2005) Murine echocardiography: a practical approach for phenotyping genetically manipulated and surgically modeled mice. J Amer Soc Echocardiog off Publn Amer Soc Echocardiog 18:982–990. doi:10.1016/j.echo.2005.05.001 CrossRef

45.

Tanaka N, Dalton N, Mao L, Rockman HA, Peterson KL, Gottshall KR, Hunter JJ, Chien KR, Ross J Jr (1996) Transthoracic echocardiography in models of cardiac disease in the mouse. Circulation 94:1109–1117. doi:10.1161/01.CIR.94.5.1109 PubMedCrossRef

46.

Thomas CV, Coker ML, Zellner JL, Handy JR, Crumbley AJ 3rd, Spinale FG (1998) Increased matrix metalloproteinase activity and selective upregulation in LV myocardium from patients with end-stage dilated cardiomyopathy. Circulation 97:1708–1715. doi:10.1161/01.CIR.97.17.1708 PubMedCrossRef

47.

Thomas M, Felcht M, Kruse K, Kretschmer S, Deppermann C, Biesdorf A, Rohr K, Benest AV, Fiedler U, Augustin HG (2010) Angiopoietin-2 stimulation of endothelial cells induces alphavbeta3 integrin internalization and degradation. J Biol Chem 285:23842–23849. doi:10.1074/jbc.M109.097543 PubMedCrossRef

48.

Towbin JA, Lowe AM, Colan SD, Sleeper LA, Orav EJ, Clunie S, Messere J, Cox GF, Lurie PR, Hsu D, Canter C, Wilkinson JD, Lipshultz SE (2006) Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA 296:1867–1876. doi:10.1001/jama.296.15.1867 PubMedCrossRef

49.

Wang L, Zheng J, Du Y, Huang Y, Li J, Liu B, Liu CJ, Zhu Y, Gao Y, Xu Q, Kong W, Wang X (2011) Cartilage oligomeric matrix protein maintains the contractile phenotype of vascular smooth muscle cells by interacting with alpha(7)beta(1) integrin. Circ Res 106:514–525. doi:10.1161/CIRCRESAHA.109.202762 CrossRef

50.

Wang L, Zheng J, Du Y, Huang Y, Li J, Liu B, Liu CJ, Zhu Y, Gao Y, Xu Q, Kong W, Wang X (2010) Cartilage oligomeric matrix protein maintains the contractile phenotype of vascular smooth muscle cells by interacting with alpha(7)beta(1) integrin. Circ Res 106:514–525. doi:10.1161/CIRCRESAHA.109.202762 PubMedCrossRef

51.

Wang W, Luo BH (2010) Structural basis of integrin transmembrane activation. J Cell Biochem 109:447–452. doi:10.1002/jcb.22427 PubMed

52.

White DE, Coutu P, Shi YF, Tardif JC, Nattel S, St Arnaud R, Dedhar S, Muller WJ (2006) Targeted ablation of ILK from the murine heart results in dilated cardiomyopathy and spontaneous heart failure. Gen Dev 20:2355–2360. doi:10.1101/gad.1458906 CrossRef

53.

Ya J, Erdtsieck-Ernste EB, de Boer PA, van Kempen MJ, Jongsma H, Gros D, Moorman AF, Lamers WH (1998) Heart defects in connexin43-deficient mice. Circ Res 82:360–366. doi:10.1161/01.RES.82.3.360 PubMedCrossRef

Title: Deficiency of cartilage oligomeric matrix protein causes dilated cardiomyopathy
Authors: Yaqian Huang
Jiahong Xia
Jingang Zheng
Bin Geng
Peng Liu
Fang Yu
Bo Liu
Hongquan Zhang
Mingjiang Xu
Ping Ye
Yi Zhu
Qingbo Xu
Xian Wang
Wei Kong
Publication date: 01-09-2013
Publisher: Springer Berlin Heidelberg
Published in: Basic Research in Cardiology / Issue 5/2013
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-013-0374-9

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Deficiency of cartilage oligomeric matrix protein causes dilated cardiomyopathy

Abstract

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