Pathogenesis of hypertrophic cardiomyopathy. Impact of growth factors on left ventricular anatomy(367 views) Migliore T, Parrella LS, Caputi A, Silvestri N, Romano R, Pace L, Imbriaco M, Losi MA, Betocchi S
Departments of Clinical Medicine and Cardiovascular and Immunological Sciences, Federico II University, Naples, Italy
Biomorphological and Functional Sciences, Federico II University, Naples, Italy
Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Via S. Pansini 5, Ed. 2, 80131 Napoli, Italy
References: Maron, B.J., Bonow, R.O., Cannon, R.O., Leon, M.B., Epstein, S.E., Hypertrophic cardiomyopathy: Interrelations of clinical manifestations, pathophysiology, and therapy (1987) N Engl J Med, 316, pp. 780-84
Marian, A.J., Roberts, R., The Molecular Genetic Basis for Hypertrophic Cardiomyopathy (2001) J Mol Cell Cardiol, 33, pp. 655-670
Watkins, H., McKenna, W.J., Thierfelder, L., Suk, H.J., Anan, R., O'Donoghue, A., Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy (1995) N Engl J Med, 332, pp. 1058-1064
Marian, A.J., Pathogenesis of diverse clinical and pathological phenotypes in hypertrophic cardiomyopathy (2000) Lancet, 355, pp. 58-60
Watkins, H., Seidman, C.E., Seidman, J.G., Feng, H.S., Sweeney, H.L., Expression and functional assessment of a truncated cardiac troponin T that causes hypertrophic cardiomyopathy.Evidence of a dominant negative action (1996) J Clin Invest, 98, pp. 2456-2461
Li, G., Borger, M.A., Williams, W.G., Weisel, R.D., Mickle, D.A.G., Wingle, E.D., Regional overexpression of insulin-like growth factor-I and transforming growth factor-beta1 in the myocardium of patients with hypertrophic obstructive cardiomyopathy (2002) J Thorac Cardiovasc Surg, 123, pp. 89-95
Ren, J., Samson, W.K., Sowers, J.R., Insulin-like Growth Factor I as a Cardiac Hormone: Physiological and Pathophysiological Implications in Heart Disease (1999) J Mol Cell Cardiol, 31, pp. 2049-2061
Li, R.K., Li, G., Mickle, D.A.G., Weisel, R.D., Merante, F., Luss, H., Overexpression of Transforming Growth Factor-β1 and Insulin-Like Growth Factor-I in Patients With Idiopathic Hypertrophic Cardiomyopathy (1997) Circulation, 96, pp. 874-881
Li, G., Li, R.K., Mickle, D.A.G., Weisel, R.D., Merante, F., Ball, W.T., Elevated insulin-like growth factor-1 and transforming growth factor-1 and their receptors in patients with idiopathic hypertrophic obstructive cardiomyopathy: A possible mechanism (1998) Circulation, 98 (SUPPL. 19), pp. II144-II149
Saeki, H., Hamada, M., Hiwada, K., Circulating Levels of Insulin Like Growth Factor-1 and Its Binding Proteins in Patients with Hypertrophic Cardiomyopathy (2002) Circ J, 66, pp. 639-644
Lim, D.S., Lutucuta, S., Bachireddy, P., Youker, K., Evans, A., Entman, M., Angiotensin II Blockade Reverses Myocardial Fibrosis in a Transgenic Mouse model of Human Hypertrophic Cardiomyopathy (2001) Circulation, 103, pp. 789-791
Marian, A.J., Senthil, V., Chen, S.N., Lombardi, R., Antifibrotic Effects of Antioxidant N-Acetylcysteine in a Mouse Model of Human Hypertrophic Cardiomyopathy Mutation (2006) J Am Coll Cardiol, 47, pp. 827-834
Patel, R., Nagueh, S.F., Tsybouleva, N., Abdellatif, M., Lutucuta, S., Kopelen, H.A., Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy (2001) Circulation, 104, pp. 317-324
Tsybouleva, N., Zhang, L., Chen, S., Patel, R., Lutucuta, S., Nemoto, S., Aldosterone, Through Novel Signaling Proteins, Is a Fundamental Molecular Bridge Between the Genetic Defect and the Cardiac Phenotype of Hypertrophic Cardiomyopathy (2004) Circulation, 109, pp. 1284-1291
Shirani, J., Pick, R., Roberts, W.C., Maron, B.J., Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death (2000) J Am Coll Cardiol, 35, pp. 36-44
Varnava, A.M., Elliott, P.M., Sharma, S., McKenna, W.J., Davies, M.J., Hypertrophic cardiomyopathy: The interrelation of disarray, fibrosis, and small vessel disease (2000) Heart, 84, pp. 476-482
Briguori, C., Betocchi, S., Romano, M., Manganelli, F., Angela Losi, M., Ciampi, Q., Exercise capacity in hypertrophic cardiomyopathy depends on left ventricular diastolic function (1999) Am J Cardiol, 84, pp. 309-315
Lombardi, R., Betocchi, S., Losi, M.A., Tocchetti, C.G., Aversa, M., Miranda, M., Myocardial Collagen Turnover in Hypertrophic Cardiomyopathy (2003) Circulation, 108, pp. 1455-1460
Fassbach, M., Schwartzkopff, B., Elevated serum markers for collagen syntesis in patients with hypertrophic cardiomyopathy and diastolic dysfunction (2005) Z Kardiol, 94, pp. 328-335
Noji, Y., Shimizu, M., Ino, H., Higashikata, T., Yamaguchi, M., Nohara, A., Increased Circulating Matrix Metalloproteinase-2 in Patients With Hypertrophic Cardiomyopathy With Systolic Dysfunction (2004) Circ J, 68, pp. 355-360
Burlew, B.S., Weber, K.T., Cardiac fibrosis as a cause of diastolic dysfunction (2002) Herz, 27, pp. 92-98
Krayenbuehl, H.P., Hess, O.M., Monrad, E.S., Schneider, J., Mall, G., Turina, M., Left ventricular myocardial structure in aortic valve disease before, intermediate, and left aortic valve replacement (1989) Circulation, 79, pp. 744-755
Maron, B. J., Bonow, R. O., Cannon, R. O., Leon, M. B., Epstein, S. E., Hypertrophic cardiomyopathy: Interrelations of clinical manifestations, pathophysiology, and therapy (1987) N Engl J Med, 316, pp. 780-84
Marian, A. J., Roberts, R., The Molecular Genetic Basis for Hypertrophic Cardiomyopathy (2001) J Mol Cell Cardiol, 33, pp. 655-670
Marian, A. J., Pathogenesis of diverse clinical and pathological phenotypes in hypertrophic cardiomyopathy (2000) Lancet, 355, pp. 58-60
Li, G., Borger, M. A., Williams, W. G., Weisel, R. D., Mickle, D. A. G., Wingle, E. D., Regional overexpression of insulin-like growth factor-I and transforming growth factor-beta1 in the myocardium of patients with hypertrophic obstructive cardiomyopathy (2002) J Thorac Cardiovasc Surg, 123, pp. 89-95
Li, R. K., Li, G., Mickle, D. A. G., Weisel, R. D., Merante, F., Luss, H., Overexpression of Transforming Growth Factor- 1 and Insulin-Like Growth Factor-I in Patients With Idiopathic Hypertrophic Cardiomyopathy (1997) Circulation, 96, pp. 874-881
Li, G., Li, R. K., Mickle, D. A. G., Weisel, R. D., Merante, F., Ball, W. T., Elevated insulin-like growth factor-1 and transforming growth factor-1 and their receptors in patients with idiopathic hypertrophic obstructive cardiomyopathy: A possible mechanism (1998) Circulation, 98 (SUPPL. 19), pp. II144-II149
Lim, D. S., Lutucuta, S., Bachireddy, P., Youker, K., Evans, A., Entman, M., Angiotensin II Blockade Reverses Myocardial Fibrosis in a Transgenic Mouse model of Human Hypertrophic Cardiomyopathy (2001) Circulation, 103, pp. 789-791
Marian, A. J., Senthil, V., Chen, S. N., Lombardi, R., Antifibrotic Effects of Antioxidant N-Acetylcysteine in a Mouse Model of Human Hypertrophic Cardiomyopathy Mutation (2006) J Am Coll Cardiol, 47, pp. 827-834
Varnava, A. M., Elliott, P. M., Sharma, S., McKenna, W. J., Davies, M. J., Hypertrophic cardiomyopathy: The interrelation of disarray, fibrosis, and small vessel disease (2000) Heart, 84, pp. 476-482
Burlew, B. S., Weber, K. T., Cardiac fibrosis as a cause of diastolic dysfunction (2002) Herz, 27, pp. 92-98
Krayenbuehl, H. P., Hess, O. M., Monrad, E. S., Schneider, J., Mall, G., Turina, M., Left ventricular myocardial structure in aortic valve disease before, intermediate, and left aortic valve replacement (1989) Circulation, 79, pp. 744-755
Pathogenesis of hypertrophic cardiomyopathy. Impact of growth factors on left ventricular anatomy
Aim. The aim of this study was to evaluate the effect of insulin-like growth factor 1 (IGF1) and transforming growth factor β-1 (TGFβ-1) on collagen turnover, left ventricular (LV) hypertrophy and on passive diastolic function of the LV in hypertrophic cardiomyopathy (HCM). Methods. This study group comprised 34 patients with non-dilated HCM. Procollagen I amino-terminal propeptide (PINP) and collagen I carboxy-terminal telopeptide (ICTP) were measured by radioimmunoassay. Matrix metalloproteinase 9 (MMP 9), IGF1 and TGF,-1 were determined by enzyme-linked immunosorbent assay. The difference in duration between transmitral forward (A) and pulmonary venous retrograde (Ar) waves, was considered as an estimate of passive diastolic function; the ratio between the peak flow velocity at rapid filling at the mitral level (E) and E' measured by tissue Doppler was considered an estimate of active diastolic function. LV mass was measured and normalized to body surface area (LVMi) by cardiac magnetic resonance imaging. Results. LVMi correlates to E/E' (r=0.597, P=0.019) and is inversely related to A-Ar (r=0.453, P=0.015). TGFβ-1 is directly related to active MMP 9 (r=0.439, P=0.012). IGF1 is directly related to PICP-ICTP (r=0.347, P=0.501), that expresses the balance between collagen I synthesis and its degradation. Conclusion. The study demonstrated that in HCM, LVMi influences active and passive diastolic dysfunction and that IGF1 stimulates collagen synthesis and TGFβ-1 is related to LV hypertrophy.
Pathogenesis of hypertrophic cardiomyopathy. Impact of growth factors on left ventricular anatomy