Mitogen-activated protein kinase inhibitors improve heart function and prevent fibrosis in cardiomyopathy caused by mutation in Lamin A/C gene

Circulation

Volumn 123, Issue 1, 2011, Pages 53-61

  Wu, Wei ^a   Muchir, Antoine ^a   Shan, Jian ^a   Bonne, Gisèle ^b,c,d   Worman, Howard J ^a  

^a Columbia University ^*  (United States)

^b INSERM   (France)

^c CNRS   (France)

^d PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

Author keywords

cardiomyopathy; LMNA; mitogen activated protein kinases; pharmacology

Indexed keywords

2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; ANTHRA[1,9 CD]PYRAZOL 6(2H) ONE; LAMIN A; LAMIN C; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; PLACEBO; STRESS ACTIVATED PROTEIN KINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARDIOMYOPATHY; CONTROLLED STUDY; DRUG ACTIVITY; ECHOCARDIOGRAPHY; GENE MUTATION; HEART FUNCTION; HEART MUSCLE FIBROSIS; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; ANTHRACENES; CARDIOMYOPATHY, DILATED; FIBROSIS; FLAVONOIDS; HEART FUNCTION TESTS; LAMIN TYPE A; MALE; MICE; MICE, TRANSGENIC; MITOGEN-ACTIVATED PROTEIN KINASES; MUTATION; MYOCARDIUM; PILOT PROJECTS; PROTEIN KINASE INHIBITORS;

EID: 78751632066     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.110.970673     Document Type: Article

References (50)

1. Taylor MRG, Carniel E, Mestroni L. Cardiomyopathy, familial dilated. Orphanet J Rare Dis. 2006;1:27.
2. Worman HJ, Fong LG, Muchir A, Young SG. Laminopathies and the long strange trip from basic cell biology to therapy. J Clin Invest. 2009;119:1825-1836.
3. Bonne G, Di Barletta MR, Varnous S, Becane HM, Hammouda EH, Merlini L, Muntoni F, Greenberg CR, Gary F, Urtizberea JA, Duboc D, Fardeau M, Toniolo D, Schwartz K. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. Nat Genet. 1999;21:285-288.
4. Muchir A, Bonne G, van der Kooi AJ, van Meegen M, Baas F, Bolhuis PA, de Visser M, Schwartz K. Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B). Hum Mol Genet. 2000;9:1453-1459.
5. Fatkin D, MacRae C, Sasaki T, Wolff MR, Porcu M, Frenneaux M, Atherton J, Vidaillet HJ Jr, Spudich S, De Girolami U, Seidman JG, Seidman C, Muntoni F, Müehle G, Johnson W, McDonough B. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. N Engl J Med. 1999; 341:1715-1724.
6. Brodsky GL, Muntoni F, Miocic S, Sinagra G, Sewry C, Mestroni L. Lamin A/C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement. Circulation. 2000;101:473-476.
7. Taylor MR, Fain PR, Sinagra G, Robinson ML, Robertson AD, Carniel E, Di Lenarda A, Bohlmeyer TJ, Ferguson DA, Brodsky GL, Boucek MM, Lascor J, Moss AC, Li WL, Stetler GL, Muntoni F, Bristow MR, Mestroni L; Familial Dilated Cardiomyopathy Registry Research Group. Natural history of dilated cardiomyopathy due to lamin A/C gene mutations. J Am Coll Cardiol. 2003;41:771-780.
8. Vytopil M, Benedetti S, Ricci E, Galluzzi G, Dello Russo A, Merlini L, Boriani G, Gallina M, Morandi L, Politano L, Moggio M, Chiveri L, Hausmanova-Petrusewicz I, Ricotti R, Vohanka S, Toman J, Toniolo D. Mutation analysis of the lamin A/C gene (LMNA) among patients with different cardiomuscular phenotypes. J Med Genet. 2003;40:e132.
9. van Tintelen JP, Hofstra RM, Katerberg H, Rossenbacker T, Wiesfeld AC, du Marchie Sarvaas GJ, Wilde AA, van Langen IM, Nannenberg EA, van der Kooi AJ, Kraak M, van Gelder IC, van Veldhuisen DJ, Vos Y, van den Berg MP. High yield of LMNA mutations in patients with dilated cardiomyopathy and/or conduction disease referred to cardiogenetics outpatient clinics. Am Heart J. 2007;154:1130-1139.
10. Cowan J, Li D, Gonzalez-Quintana J, Morales A, Hershberger RE. Morphological analysis of 13 LMNA variants identified in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy. Circ Cardiovasc Genet. 2010;3:6-14.
11. van Berlo JH, de Voogt WG, van der Kooi AJ, van Tintelen JP, Bonne G, Yaou RB, Duboc D, Rossenbacker T, Heidbüchel H, de Visser M, Crijns HJ, Pinto YM. Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: do lamin A/C mutations portend a high risk of sudden death? J Mol Med. 2005;83:79-83.
12. Pasotti M, Klersy C, Pilotto A, Marziliano N, Rapezzi C, Serio A, Mannarino S, Gambarin F, Favalli V, Grasso M, Agozzino M, Campana C, Gavazzi A, Febo O, Marini M, Landolina M, Mortara A, Piccolo G, Vigano M, Tavazzi L, Arbustini E. Long-term outcome and risk stratification in dilated cardiolaminopathies. J Am Coll Cardiol. 2008;52: 1250-1260.
13. Arimura T, Helbling-Leclerc A, Massart C, Varnous S, Niel F, Lacene E, Fromes Y, Toussaint M, Mura AM, Keller DI, Amthor H, Isnard R, Malisses M, Schwartz K, Bonne G. Mouse model carrying H222P-lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies. Hum Mol Genet. 2005; 14:155-169.
14. Muchir A, Pavlidis P, Decostre V, Herron AJ, Arimura T, Bonne G, Worman HJ. Activation of MAPK pathway links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy. J Clin Invest. 2007;117:1282-1293.
15. Muchir A, Shan J, Bonne G, Lehnart SE, Worman HJ. Inhibition of extracellular signal-regulate kinase signaling to prevent cardiomyopathy caused by mutation in the gene encoding A-type lamins. Hum Mol Genet. 2009;18:241-247.
16. Wu W, Shan J, Bonne G, Worman HJ, Muchir A. Pharmacological inhibition of c-Jun N-terminal kinase prevents cardiomyopathy caused by mutation in LMNA gene. Biochim Biophys Acta. 2010;1802:632-638.
17. Yoshimine K, Horiuchi M, Suzuki S, Kobayashi K, Abdul JM, Masuda M, Tomomura M, Ogawa Y, Itoh H, Nakao K, Osame M, Saheki T. Altered expression of atrial natriuretic peptide and contractile protein genes in hypertrophied ventricles of JVS mice with systemic carnitine deficiency. J Mol Cell Cardiol. 1997;29:571-578.
18. Takahashi T, Allen PD, Izumo S. Expression of A-, B-, and C-type natriuretic peptide genes in failing and developing human ventricles: correlation with expression of the Ca(2 + )-ATPase gene. Circ Res. 1992; 71:9-17.
19. Hwang JJ, Allen PD, Tseng GC, Lam CW, Fananapazir L, Dzau VJ, Liew CC. Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure. Physiol Genomics. 2002;10: 31-44.
20. Yung CK, Halperin VL, Tomaselli GF, Winslow RL. Gene expression profiles in end-stage human idiopathic dilated cardiomyopathy: altered expression of apoptotic and cytoskeletal genes. Genomics. 2004;83: 281-297.
21. Van Tintelen PJ, Tio RA, Kerstjens-Frederikse WS, van Berlo JH, Boven LG, Suurmeijer AJH, White SJ, den Dunnen JT, te Meerman GJ, Vos YJ, van der Hout AH, Osinga J, van den Berg MP, van Verhuisen DJ, Buys CHCM, Hofstra RMW, Pinto YM. Severe myocardial fibrosis caused by a deletion of the 5' end of the lamin A/C gene. J Am Coll Cardiol. 2007;49:2430-2439.
22. Raman SV, Sparks EA, Baker PM, McCarthy B, Wooley CF. Mid-myocardial fibrosis by cardiac magnetic resonance in patients with lamin A/C cardiomyopathy: possible substrate for diastolic dysfunction. J Cardiovac Magn Res. 2007;9:907-913.
23. Nikolova V, Leimena C, McMahon AC, Tan JC, Chandar S, Jogia D, Kesteven SH, Michalicek J, Otway R, Verheyen F, Rainer S, Stewart CL, Martin D, Feneley MP, Fatkin D. Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C-deficient mice. J Clin Invest. 2004;113:357-369.
24. Chandar S, Yeo LZ, Leimena C, Tan JC, Xiao XH, Nikolova-Krstevski V, Yasuoka Y, Gardiner-Garden M, Wu J, Kesteven S, Karlsdotter L, Natarajan S, Carlton A, Rainer S, Feneley MP, Fatkin D. Effects of mechanical stress and carvedilol in lamin A/C-deficient dilated cardiomyopathy. Circ Res. 2010;106:573-582.
25. Arimura T, Sato R, Machida N, Bando H, Zhan DY, Morimoto S, Tanaka R, Yamane Y, Bonne G, Kimura A. Improvement of left ventricular dysfunction and of survival prognosis of dilated cardiomyopathy by administration of calcium sensitizer SCH00013 in a mouse model. J Am Coll Cardiol. 2010;55:1502-1508.
26. Swynghedauw B. Molecular mechanisms of myocardial remodelling. Physiol Rev. 1999;79:215-262.
27. Brown RD, Ambler SK, Mitchell MD, Long CS. The cardiac fibroblasts: therapeutic target in myocardial remodelling and failure. Annu Rev Pharmacol Toxicol. 2005;45:657-687.
28. Sleight P. Angiotensin II and trials of cardiovascular outcomes. Am J Cardiol. 2002;89:11-16.
29. Fox KM. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPE study). Lancet. 2003;362:782-788.
30. Brilla CG, Funck RC, Rupp H. Lisinopril-mediated regression of myocardial fibrosis in patients with hypertensive heart disease. Circulation. 2000;102:1388-1393.
31. Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergen J, Yusuf S, Pocock S. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003;362:759-766. (Pubitemid 37093915)
32. Diez J, Querejeta R, Lopez B, Gonzalez A, Larman M, Martinez Ubago JL. Losartan-dependent regression of myocardial fibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients. Circulation. 2002;105:2512-2517.
33. Lopez B, Gonzalez A, Beaumont J, Querejeta R, Larman M, Diez J. Identification of a potential cardiac antifibrotic mechanism of torasemide in patients with chronic heart failure. J Am Coll Cardiol. 2007;50:859-867.
34. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure: Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341:709-717.
35. Pitt B, Remme W, Zammad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309-1321.
36. Zannad F, Alla F, Dousset B, Perez A, Pitt B. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the Randomized Aldactone Evaluation Study (RALES). Circulation. 2000;102: 2700-2706.
37. Yoon S, Seger R. The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions. Growth Factors. 2006;24: 21-44.
38. Zanolla L, Zardini P. Selection of endpoints for heart failure clinical trials. Eur J Heart Fail. 2003;5:717-723.
39. White HD, Norris, RM Brown MA, Brandt PW, Whitlock RM, Wild CJ. Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation. 1987;76:44-51.
40. Hamer AW, Takayama M, Abraham KA, Roche AH, Kerr AR, Williams BF, Ramage MC, White HD. End-systolic volume and long-term survival after coronary artery bypass graft surgery in patients with impaired left ventricular function. Circulation. 1994;90:2899-2904.
41. Heywood JT, Elatre W, Pai RG, Fabbri S, Huiskes B. Simple clinical criteria to determine the prognosis of heart failure. J Cardiovasc Pharmacol Ther. 2005;10:173-180.
42. Ikeda Y, Ross J. Models of dilated cardiomyopathy in the mouse and the hamster. Curr Opin Cardiol. 2000;15:197-201.
43. Khurana TS, Davies KE. Pharmacological strategies for muscular dystrophy. Nat Rev Drug Discov. 2003;2:379-390.
44. Bhatnagar S, Kumar A. Therapeutic targeting of signalling pathways in muscular dystrophy. J Mol Med. 2010;88:155-166.
45. Allen LF, Sebolt-Leopold J, Meyer MB. Cl-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK). Semin Oncol. 2003;30: 105-116.
46. Brown AP, Carlson TCG, Loi CM, Graziano MJ. Pharmacodynamic and toxicokinetic evaluation of the novel MEK inhibitor, PD0325901, in the rat following oral and intravenous administration. Cancer Chemother Pharmacol. 2007;59:671-679.
47. Lorusso P, Krishnamurthi S, Rinehart JR, Nabell L, Croghan G, Varterasian M, Sadis SS, Menon S, Leopold J, Meyer MB. A phase 1-2 clinical study of a second generation oral MEK inhibitor, PD0325901 in patients with advanced cancer [abstract]. J Clin Oncol. 2005;23:3011.
48. Menon SS, Whitfield LR, Sadis S, Meyer MB, Leopold J, Lorusso PM, Krishnamurthi S, Rinehart JR, Nabell L, Croghan G. Pharmacokinetics (PK) and pharmacodynamics (PD) of PD0325901, a second generation MEK inhibitor after multiple oral doses of PD0325901 to advanced cancer patients [abstract]. J Clin Oncol. 2005;23:3066.
49. Adjei AA, Cohen RB, Franklin W, Morris C, Wilson D, Molina JR, Hanson LJ, Gore L, Chow L, Leong S, Maloney L, Gordon G, Simmons H, Marlow A, Litwiler K, Brown S, Poch G, Kane K, Haney J, Eckhardt SG. Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers. J Clin Oncol. 2008;26:2139-2146.
50. Bogoyevitch MA, Ngoei KR, Zhao TT, Yeap YY, Ng DC. c-Jun N-terminal kinase (JNK) signaling: recent advances and challenges. Biochim Biophys Acta. 2010;3:463-475.