Comparison of the effects of a truncating and a missense MYBPC3 mutation on contractile parameters of engineered heart tissue

Journal of Molecular and Cellular Cardiology

Volumn 97, Issue , 2016, Pages 82-92

  Wijnker, Paul J M ^a,b,c   Friedrich, Felix W ^a,b   Dutsch, Alexander ^a,b   Reischmann, Silke ^a,b   Eder, Alexandra ^a,b   Mannhardt, Ingra ^a,b   Mearini, Giulia ^a,b   Eschenhagen, Thomas ^a,b   van der Velden, Jolanda ^c   Carrier, Lucie ^a,b  

^a UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^b DZHK GERMAN CENTRE FOR CARDIOVASCULAR RESEARCH   (Germany)

^c VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Cardiac myosin binding protein C; Engineered heart tissue; Haploinsufficiency; Hypertrophic cardiomyopathy; Missense mutation; Truncating mutation

Indexed keywords

CALCIUM ION; CARRIER PROTEIN; MYOSIN-BINDING PROTEIN C;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CARDIAC MUSCLE CELL; CONTROLLED STUDY; ENGINEERED HEART TISSUE; GENE; GENE EXPRESSION; GENE INACTIVATION; GENE TARGETING; HAPLOINSUFFICIENCY; HEART CONTRACTION; MISSENSE MUTATION; MOUSE; MYBPC3 GENE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; ANIMAL; CARDIAC MUSCLE; CELL LINE; GENETICS; GENOTYPE; HUMAN; HYPERTROPHIC CARDIOMYOPATHY; KNOCKOUT MOUSE; METABOLISM; MUTATION; PATHOLOGY; SARCOMERE; TISSUE ENGINEERING;

ANIMALS; CARDIOMYOPATHY, HYPERTROPHIC; CARRIER PROTEINS; CELL LINE; GENE EXPRESSION; GENOTYPE; HAPLOINSUFFICIENCY; HUMANS; MICE; MICE, KNOCKOUT; MUTATION; MUTATION, MISSENSE; MYOCARDIAL CONTRACTION; MYOCARDIUM; PHENOTYPE; SARCOMERES; TISSUE ENGINEERING;

EID: 84969263643     PISSN: 00222828     EISSN: 10958584     Source Type: Journal    
DOI: 10.1016/j.yjmcc.2016.03.003     Document Type: Article

References (55)

1. Maron B.J., Gardin J.M., Flack J.M., Gidding S.S., Kurosaki T.T., Bild D.E. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults. Circulation 1995, 92:785-789.
2. Elliott P., Andersson B., Arbustini E., Bilinska Z., Cecchi F., Charron P., et al. Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur. Heart J. 2008, 29:270-276.
3. Schlossarek S., Mearini G., Carrier L. Cardiac myosin-binding protein C in hypertrophic cardiomyopathy: mechanisms and therapeutic opportunities. J. Mol. Cell. Cardiol. 2011, 50:613-620.
4. Friedrich F.W., Carrier L. Genetics of hypertrophic and dilated cardiomyopathy. Curr. Pharm. Biotechnol. 2012, 13:2467-2476.
5. Ho C.Y., Charron P., Richard P., Girolami F., Van Spaendonck-Zwarts K.Y., Pinto Y. Genetic advances in sarcomeric cardiomyopathies: state of the art. Cardiovasc. Res. 2015, 105:397-408.
6. Richard P., Charron P., Carrier L., Ledeuil C., Cheav T., Pichereau C., et al. Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation 2003, 107:2227-2232.
7. Germans T., Wilde A.A., Dijkmans P.A., Chai W., Kamp O., Pinto Y.M., et al. Structural abnormalities of the inferoseptal left ventricular wall detected by cardiac magnetic resonance imaging in carriers of hypertrophic cardiomyopathy mutations. J. Am. Coll. Cardiol. 2006, 48:2518-2523.
8. Germans T., Russel I.K., Gotte M.J., Spreeuwenberg M.D., Doevendans P.A., Pinto Y.M., et al. How do hypertrophic cardiomyopathy mutations affect myocardial function in carriers with normal wall thickness? Assessment with cardiovascular magnetic resonance. J. Cardiovasc. Magn. Reson. 2010, 12:13.
9. Ho C.Y., Carlsen C., Thune J.J., Havndrup O., Bundgaard H., Farrohi F., et al. Echocardiographic strain imaging to assess early and late consequences of sarcomere mutations in hypertrophic cardiomyopathy. Circ. Cardiovasc. Genet. 2009, 2:314-321.
10. Michels M., Soliman O.I., Kofflard M.J., Hoedemaekers Y.M., Dooijes D., Majoor-Krakauer D., et al. Diastolic abnormalities as the first feature of hypertrophic cardiomyopathy in Dutch myosin-binding protein C founder mutations. J. Am. Coll. Cardiol. Img. 2009, 2:58-64.
11. Behrens-Gawlik V., Mearini G., Gedicke-Hornung C., Richard P., Carrier L. MYBPC3 in hypertrophic cardiomyopathy: from mutation identification to RNA-based correction. Pflugers Arch. 2014, 466:215-223.
12. Carrier L., Mearini G., Stathopoulou K., Cuello F. Cardiac myosin-binding protein C (MYBPC3) in cardiac pathophysiology. Gene 2015, 573:188-197.
13. Decker R.S., Decker M.L., Kulikovskaya I., Nakamura S., Lee D.C., Harris K., et al. Myosin-binding protein C phosphorylation, myofibril structure, and contractile function during low-flow ischemia. Circulation 2005, 111:906-912.
14. Herron T.J., Rostkova E., Kunst G., Chaturvedi R., Gautel M., Kentish J.C. Activation of myocardial contraction by the N-terminal domains of myosin binding protein-C. Circ. Res. 2006, 98:1290-1298.
15. Kuster D.W., Sequeira V., Najafi A., Boontje N.M., Wijnker P.J., Witjas-Paalberends E.R., et al. GSK3beta phosphorylates newly identified site in the proline-alanine-rich region of cardiac myosin-binding protein C and alters cross-bridge cycling kinetics in human: short communication. Circ. Res. 2013, 112:633-639.
16. Pohlmann L., Kroger I., Vignier N., Schlossarek S., Kramer E., Coirault C., et al. Cardiac myosin-binding protein C is required for complete relaxation in intact myocytes. Circ. Res. 2007, 101:928-938.
17. Stelzer J.E., Dunning S.B., Moss R.L. Ablation of cardiac myosin-binding protein-C accelerates stretch activation in murine skinned myocardium. Circ. Res. 2006, 98:1212-1218.
18. Stelzer J.E., Patel J.R., Moss R.L. Protein kinase A-mediated acceleration of the stretch activation response in murine skinned myocardium is eliminated by ablation of cMyBP-C. Circ. Res. 2006, 99:884-890.
19. Cazorla O., Szilagyi S., Vignier N., Salazar G., Kramer E., Vassort G., et al. Length and protein kinase A modulations of myocytes in cardiac myosin binding protein C-deficient mice. Cardiovasc. Res. 2006, 69:370-380.
20. Chen P.P., Patel J.R., Rybakova I.N., Walker J.W., Moss R.L. Protein kinase A-induced myofilament desensitization to Ca(2+) as a result of phosphorylation of cardiac myosin-binding protein C. J. Gen. Physiol. 2010, 136:615-627.
21. Harris S.P., Lyons R.G., Bezold K.L. In the thick of it: HCM-causing mutations in myosin binding proteins of the thick filament. Circ. Res. 2011, 108:751-764.
22. Marston S., Copeland O., Jacques A., Livesey K., Tsang V., McKenna W.J., et al. Evidence from human myectomy samples that MYBPC3 mutations cause hypertrophic cardiomyopathy through haploinsufficiency. Circ. Res. 2009, 105:219-222.
23. van Dijk S.J., Dooijes D., dos Remedios C., Michels M., Lamers J.M., Winegrad S., et al. Cardiac myosin-binding protein C mutations and hypertrophic cardiomyopathy: haploinsufficiency, deranged phosphorylation, and cardiomyocyte dysfunction. Circulation 2009, 119:1473-1483.
24. Carrier L, Mearini G, Stathopoulou K, Cuello F. Cardiac myosin-binding protein C (MYBPC3) in cardiac pathophysiology. Gene. 2015; (in press).
25. Sequeira V., Wijnker P.J., Nijenkamp L.L., Kuster D.W., Najafi A., Witjas-Paalberends E.R., et al. Perturbed length-dependent activation in human hypertrophic cardiomyopathy with missense sarcomeric gene mutations. Circ. Res. 2013, 112:1491-1505.
26. Beuckelmann D.J., Nabauer M., Erdmann E. Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure. Circulation 1992, 85:1046-1055.
27. Alders M., Jongbloed R., Deelen W., van den Wijngaard A., Doevendans P., Ten Cate F., et al. The 2373insG mutation in the MYBPC3 gene is a founder mutation, which accounts for nearly one-fourth of the HCM cases in the Netherlands. Eur. Heart J. 2003, 24:1848-1853.
28. Christiaans I., Nannenberg E.A., Dooijes D., Jongbloed R.J., Michels M., Postema P.G., et al. Founder mutations in hypertrophic cardiomyopathy patients in the Netherlands. Neth. Hear. J. 2010, 18:248-254.
29. Moolman J.A., Reith S., Uhl K., Bailey S., Gautel M., Jeschke B., et al. A newly created splice donor site in exon 25 of the MyBP-C gene is responsible for inherited hypertrophic cardiomyopathy with incomplete disease penetrance. Circulation 2000, 101:1396-1402.
30. Niimura H., Bachinski L.L., Sangwatanaroj S., Watkins H., Chudley A.E., McKenna W., et al. Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy. N. Engl. J. Med. 1998, 338:1248-1257.
31. Girolami F., Olivotto I., Passerini I., Zachara E., Nistri S., Re F., et al. A molecular screening strategy based on beta-myosin heavy chain, cardiac myosin binding protein C and troponin T genes in Italian patients with hypertrophic cardiomyopathy. J. Cardiovasc. Med. (Hagerstown) 2006, 7:601-607.
32. Olivotto I., Girolami F., Sciagra R., Ackerman M.J., Sotgia B., Bos J.M., et al. Microvascular function is selectively impaired in patients with hypertrophic cardiomyopathy and sarcomere myofilament gene mutations. J. Am. Coll. Cardiol. 2011, 58:839-848.
33. Eschenhagen T., Mummery C., Knollmann B.C. Modelling sarcomeric cardiomyopathies in the dish: from human heart samples to iPSC cardiomyocytes. Cardiovasc. Res. 2015, 105:424-438.
34. Hansen A., Eder A., Bonstrup M., Flato M., Mewe M., Schaaf S., et al. Development of a drug screening platform based on engineered heart tissue. Circ. Res. 2010, 107:35-44.
35. Hirt M.N., Hansen A., Eschenhagen T. Cardiac tissue engineering: state of the art. Circ. Res. 2014, 114:354-367.
36. Carrier L., Knoll R., Vignier N., Keller D.I., Bausero P., Prudhon B., et al. Asymmetric septal hypertrophy in heterozygous cMyBP-C null mice. Cardiovasc. Res. 2004, 63:293-304.
37. Mearini G., Stimpel D., Geertz B., Weinberger F., Kramer E., Schlossarek S., et al. Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice. Nat. Commun. 2014, 5:5515.
38. Stohr A., Friedrich F.W., Flenner F., Geertz B., Eder A., Schaaf S., et al. Contractile abnormalities and altered drug response in engineered heart tissue from Mybpc3-targeted knock-in mice. J. Mol. Cell. Cardiol. 2013, 63:189-198.
39. Friedrich F.W., Wilding B.R., Reischmann S., Crocini C., Lang P., Charron P., et al. Evidence for FHL1 as a novel disease gene for isolated hypertrophic cardiomyopathy. Hum. Mol. Genet. 2012, 21:3237-3254.
40. Crocini C., Arimura T., Reischmann S., Eder A., Braren I., Hansen A., et al. Impact of ANKRD1 mutations associated with hypertrophic cardiomyopathy on contraction parameters of engineered heart tissue. Basic Res. Cardiol. 2013, 108:349.
41. Hirt M.N., Boeddinghaus J., Mitchell A., Schaaf S., Bornchen C., Muller C., et al. Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation. J. Mol. Cell. Cardiol. 2014, 74:151-161.
42. 2+ transients in engineered heart tissue. Am. J. Physiol. Heart Circ. Physiol. 2014, 306:H1353-H1363.
43. Flenner F., Friedrich F.W., Ungeheuer N., Christ T., Geertz B., Reischmann S., et al. Ranolazine antagonizes catecholamine-induced dysfunction in isolated cardiomyocytes, but lacks long-term therapeutic effects in vivo in a mouse model of hypertrophic cardiomyopathy. Cardiovasc. Res. 2015.
44. de Lange W.J., Grimes A.C., Hegge L.F., Ralphe J.C. Ablation of cardiac myosin-binding protein-C accelerates contractile kinetics in engineered cardiac tissue. J. Gen. Physiol. 2013, 141:73-84.
45. de Lange W.J., Hegge L.F., Grimes A.C., Tong C.W., Brost T.M., Moss R.L., et al. Neonatal mouse-derived engineered cardiac tissue: a novel model system for studying genetic heart disease. Circ. Res. 2011, 109:8-19.
46. Carrier L., Schlossarek S., Willis M.S., Eschenhagen T. The ubiquitin-proteasome system and nonsense-mediated mRNA decay in hypertrophic cardiomyopathy. Cardiovasc. Res. 2010, 85:330-338.
47. Sarikas A., Carrier L., Schenke C., Doll D., Flavigny J., Lindenberg K.S., et al. Impairment of the ubiquitin-proteasome system by truncated cardiac myosin binding protein C mutants. Cardiovasc. Res. 2005, 66:33-44.
48. Schlossarek S., Frey N., Carrier L. Ubiquitin-proteasome system and hereditary cardiomyopathies. J. Mol. Cell. Cardiol. 2014, 71:25-31.
49. Korte F.S., McDonald K.S., Harris S.P., Moss R.L. Loaded shortening, power output, and rate of force redevelopment are increased with knockout of cardiac myosin binding protein-C. Circ. Res. 2003, 93:752-758.
50. Tong C.W., Stelzer J.E., Greaser M.L., Powers P.A., Moss R.L. Acceleration of crossbridge kinetics by protein kinase A phosphorylation of cardiac myosin binding protein C modulates cardiac function. Circ. Res. 2008, 103:974-982.
51. Fabiato A. Myoplasmic free calcium concentration reached during the twitch of an intact isolated cardiac cell and during calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned cardiac cell from the adult rat or rabbit ventricle. J. Gen. Physiol. 1981, 78:457-497.
52. + sensitive tension due to partial extraction of C-protein from rat skinned cardiac myocytes and rabbit skeletal muscle fibers. J. Gen. Physiol. 1991, 97:1141-1163.
53. 2+ sensitivity and diastolic dysfunction as early consequences of Mybpc3 mutation in heterozygous knock-in mice. J. Mol. Cell. Cardiol. 2012, 52:1299-1307.
54. Bahrudin U., Morisaki H., Morisaki T., Ninomiya H., Higaki K., Nanba E., et al. Ubiquitin-proteasome system impairment caused by a missense cardiac myosin-binding protein C mutation and associated with cardiac dysfunction in hypertrophic cardiomyopathy. J. Mol. Biol. 2008, 384:896-907.
55. Millat G., Bouvagnet P., Chevalier P., Dauphin C., Jouk P.S., Da Costa A., et al. Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy. Eur. J. Med. Genet. 2010, 53:261-267.