Cardiac Hypertrophy : Molecular Biological Approach

Shin-ichirou IMAMURA

doi:10.11276/jsvc1984.30.35

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Keywords: cardiac hypertrophy, hypertrophic cardiomyopathy, molecular biology, myosin heavy chain, signal transduction pathway

JOURNAL FREE ACCESS

1997 Volume 30 Issue 2 Pages 35-47

DOI https://doi.org/10.11276/jsvc1984.30.35

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Published: 1997 Received: - Available on J-STAGE: September 17, 2009 Accepted: - Advance online publication: - Revised: -
Correction information
Date of correction: September 17, 2009 Reason for correction: - Correction: TITLE Details: [in Japanese]

Date of correction: September 17, 2009 Reason for correction: - Correction: SUBTITLE Details: [in Japanese]

Date of correction: September 17, 2009 Reason for correction: - Correction: CITATION Details: Wrong : 1) Laks, M. M., Morady, F., Garner, D, and H. J. Swan C. (1974) : Temporal changes in canine right ventricular volume, mass, cell size, and sarcomere length after binding the pulmonary artery. Cardiovasc. Res., 8, 106-111.
2) Hoh, J. F. Y., McGrath, P. A. and H. T. Hale (1978) : Electrophoretic analysis of multiple forms of rat cardiac myosin. Effect of hypophysectomy and thyroxine replacement. J. Mol. Cell. CardioL, 10, 1053-1076.
3) Mahdavi, V., Periasamy, V. and B. Nadal-Ginard (1982) : Molecular characterization of two myosin heavy chain genes expressed in the adult heart.Nature, 297, 659-665.
4) Dechesne, C. A., Bouvagnet, P., Walzthony. D. and J. J. Leger (1987) : Visualization of cardiac ventricular myosin heavy chain homodimers and heterodimers by monoclonal antibody epitope mapping. J. Cell. Biol., 105, 3031-3037.
5) Imamura, S., Matsuoka, R., Hiratsuka, E., Kimura, M., Nakanishi, T., Nishikawa, T., Furutani, Y. and A. Takao (1991) : Adaptational changes of MHC gene expression and isozyme transition in cardiac overloading. Am. J. Physiol, 260, H73-H79.
6) Chilian, W. M. and M. L. Marcus (1987) : Coronary vascular adaptations to myocardial hypertrophy. Annu. Rev. Physiol., 49, 477-487.
7) Bache R. J. (1988) : Effects of hypertrophy on the coronary circulation. Prog. Cardiovasc. Dis., 30, 403-440, 1988.
8) Haneda, T., Ichihara, K., Abiko, Y. and S. Onodera, (1986) : Functional and metabolic responses to ischemia in the perfused heart isolated from nor-motensive and spontaneously hypertensive rats. Jpn. Circ. J., 50, 607-611.
9) Mercadier, J. J., Lompre, A.-M., Duc, P., Boheler, K. R., Fraysse J.-B., Wisnewsky, C., Allen, P. D., Komajda, M. and K. Schwarts (1990) : Altered sarcoplasmic reticulum Ca²⁺-ATPase gene expression n the human ventricle during end-stage heart failure. J. Clin. Invest., 85, 305-309.
10) Cutilletta, A. F., Dowell, R. T., Rudnik, M., Arcilla, R. A. and R. Zak (1975) : Regression of myocardial hypertrophy. I. Experimental model, changes in heart weight, nucleic acids and collagen. J. Mot. Cell. Cardiol., 7, 767-781.
11) Panidis, JP., Kotler, M. N., Ren, J. F., Minitz, G. S., Ross, J. and P. Kalman, (1984) : Development and regression of left ventricular hypertrophy. J. Am. Coll. Cardiol., 3, 1309-1320.
12) Isoyama, S., Ito, N., Kuroha, M. and T. Takishima (1989) : Complete reversibility of physiological coronary vascular abnormalities in hypertrophied hearts produced by pressure-overload in the rat. J. Clin. Invest., 84, 288-294.
13) Imamura, S., Takao, A. and R. Matsuoka (1996) : Regression speed of cardiac myosin heavy chain isozyme V3 in loaded right or left ventricle after relief of the load. Eur., J. Clin., Invest., 26, 240-246.
14) Simpson, P.(1985) : Stimulation of hypertrophy of cultured neonatal rat heart cells through an bladrenergic receptor and induction of beating through an al-and b1-adrenergic receptor interaction. Circ. Res., 56, 884-894.
15) Henrich, C. J. and P. C. Simpson (1988) : Differential acute and chronic response of protein kinase in cultured neonatal rat heart myocytes to a 1-adrenergic and phorbolester stimulation. J. MoL Cell. Cardiol., 20, 1081-1085.
16) Haneda, T. and P. J. McDermott (1991) : Stimulation of ribosomal RNA synthesis during hypertrophic growth of cultured heart cells by phorbol ester. Mol. Cell. Biochem., 104, 169-177.
17) Xenophantos, X., Watson, P. A., Chua, B. H. L., Haneda, T. and H. E. Morgan (1989) : Increased cyclic AMP content accelerates protein synthesis in rat heart. Circ. Res., 65, 647-656.
18) Imamura, S., Kimura, M., Hiratsuka, E., Takao, A. and R. Matsuoka (1992) : Effect of caffeine on expression of cardiac myosin heavy chain gene in adult hypothyroid and fetal rats. Circ. Res., 71, 1031-1038.
19) Matsuoka, R., Uno, H., Tanaka., H., Kerr, C. S., Nakazawa, K. and b. Nadal-Ginard (1987) : Caffeine induces cardiac and other malformations in the rat. Am, J. Med. Genet., 3 (suppl), 433-443.
20) Miyata, S. and T. Haneda (1994) : Hypertrophic growth of cultured neonatal rat heart cells mediated by typel angiotensin II receptor. Am. J. Physiol., 266, H2443-H2451.
21) Pennica, D., King., K. L., Shaw, K. J., Luis, E., Rullamas, J., Luoh, S. M., Darbonne, W. C., Knutzon, D. S., Yen, R., Chien, K. R., Baker, J. B.and W. I. Wood (1995) : Expression cloning of cardiotrophin-1, a cytokine that induces cardiac myocyte hypertrophy. Proc. Natl. Acad. Sci. USA, 92, 1142-1146.
22) Imamura, S., Matsuoka, R., Hiratsuka, E., Kimura, M., Nishikawa, T. and A. Takao (1990) : Local response to cardiac overload on myosin heavy chain gene expression and isozyme transition. Circ. Res., 66, 1067-1073.
23) Komuro, I. and Y. Yazaki (1993) : Control of cardiac gene expression by mechanical stress. Annu. Rev. Physiol., 55, 55-75.
24) Komuro, I., Katoh, Y., Kaida, T., Shibazaki, Y., Kurabayashi, M., Hoh, E., Takaku, F. and Y. Yazaki (1991) : Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes. Possible role of protein kinase C activation. J. Biol. Chem., 266, 1265-1268.
25) Sadoshima, J., Xu, Y., Slayter, H. S.and S. Izumo (1993) : Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell., 75, 977-984.
26) Richardson, P., McKenna, W., Bristow, M., Maisch, B., Mautner B, O'Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I and P. Nordet (1996) : Report of the 1995 world health organization/international society and federation of cardiology task force on the definition and classification of cardiomyopathies. Circulation, 93, 841-842.
27) Jarcho, J. A., McKenna, W., Pare, J. A., Solomon, S. D., Holcombe, R. F., Dickie, S., Levi, T., Donis-Keller, H., Seidman, J. G. and C. E. Seidman (1989) : Mapping a gene for familial hypertrophic cardiomyopathy to chromosome 14q1. New Engl. J. Med., 321, 1372-1378.
28) Geisterfer-Lowrance, A. A., Kass, S., Tanigawa, G., Vosberg, H. P., McKenna, W., Seidman, C. E.,and J. G. Seidman (1990) : A molecular basis for familial hypertrophic cardiomyopathy : A b cardiac myosin heavy chain gene missense mutation. Cell, 62, 999-1006.
29) Tanigawa, G., Jarcho, J. A., Kass, S., Solomon, S. D., Vosberg, H. P., Seidman, J. G. and C. E. Seidman (1990) : A molecular basis for familial hypertrophic cardiomyopathy : An a/b cardiac myosin heavy chain hybrid gene. Cell, 62, 991-998.
30) Arai, S., Matsuoka, R., Hirayama, K., Sakurai, H., Tamura, M., Ozawa, T., Kimura, M., Imamura, S., Furutani, Y., Joh-o, K., Kawana, M., Takao, A., Hosoda, S. and K. Momma (1995) : Missense mutation of the b-cardiac myosin heavy-chaingene in hypertrophic cardiomyopathy. Am. J. Med. Genet., 58, 267-276.
31) Thierfelder, L., MacRae, C., Watkins, H., Tomfo-hrde, J., Williams, M., McKenna, W., Bohm, K., Noeske, G., Schlepper, M., Bowcock, A., Vosberg, H.-P., Seidman, J. G. and C. Seidman (1993) : A familial hypertrophic cardiomyopathy locus maps to chromosome 15q2. Proc. Natl. Acad. Sci., U. S. A., 90, 6270-6274.
32) Watkins, H., MacRae, C., Thierfelder, L., Chou, Y. H., Frenneaux, M., McKenna, W., Seidman, J. G. and C. E. Seidman (1993) : A disease locus for familial hypertrophic cardiomyopathy maps to chromosome 1q3. Nature Genet., 32, 333-337.
33) Thierfelder, L., Watkins, H., MacRae, C., Lamas R., McKenna, W., Vosberg. H. P., Seidman. J. G., and C. E. Seidman (1990) : α-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy. A. disease of the sarcomere. Cell, 62, 991-998.
34) Watkins, H., Conner, D., Thierfelder, L., Jarcho, J. A., MacRae, C., McKenna, W. J., Maron, B. J., Seidman, J. G. and C. E. Seidman (1995) : Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nature Genet., 11, 434-437.
35) Bonne, G., Carrier, L., Bercovici, J., Cruaud, C., Richard, P., Hainque, B., Gautel, M., Labeit, S., James ,M., Beckmann, J., Weissenbach, J., Vosberg, H.-P., Fiszman, M., Komajda, M. and K. Schwartz (1995) : Cardiac myosin binding protein-C gene splice acceptor site mutation is associated with familial hypertrophic cardiomyopathy. Nature Genet., 11, 438-441.
36) Cuda, G., Fananapazir, L., Zhu, W. S., Sellers, J. R. and N. D. Epstein (1993) : Skeletal muscle expression and abnormal function of b-myosin in hypertrophic cardiomyopathy. J. Clin. Invest., 91, 2861-2865.
37) Lankford, EB., Epstein, N. D., Fananapazir, L. and H. L. Sweeney (1995) : Abnormal contractile properties of muscle fibers expressing b-myosin heavy chain gene mutations in patients with hypertrophic cardiomyopathy. J. Clin. Invest., 95, 1409-1414.
38) Fukushima, Y., Ohashi, H., Wakui, K., Nishida, T. and T. Oh-ishi (1992) : A rapid method for starting a culture for the establishment of Epstein-Barr virus-transformed human lymphoblastoid cell lines. Jpn. J. Human Genet., 37, 149-150.

Right : 1) Laks, M. M., Morady, F., Garner, D, and H. J. Swan C. (1974) : Temporal changes in canine right ventricular volume, mass, cell size, and sarcomere length after binding the pulmonary artery. Cardiovasc. Res., 8, 106-111.
2) Hoh, J. F. Y., McGrath, P. A. and H. T. Hale (1978) : Electrophoretic analysis of multiple forms of rat cardiac myosin. Effect of hypophysectomy and thyroxine replacement. J. Mol. Cell. Cardiol, 10, 1053-1076.
3) Mahdavi, V., Periasamy, V. and B. Nadal-Ginard (1982) : Molecular characterization of two myosin heavy chain genes expressed in the adult heart.Nature, 297, 659-665.
4) Dechesne, C. A., Bouvagnet, P., Walzthony. D. and J. J. Leger (1987) : Visualization of cardiac ventricular myosin heavy chain homodimers and heterodimers by monoclonal antibody epitope mapping. J. Cell. Biol., 105, 3031-3037.
5) Imamura, S., Matsuoka, R., Hiratsuka, E., Kimura, M., Nakanishi, T., Nishikawa, T., Furutani, Y. and A. Takao (1991) : Adaptational changes of MHC gene expression and isozyme transition in cardiac overloading. Am. J. Physiol, 260, H73-H79.
6) Chilian, W. M. and M. L. Marcus (1987) : Coronary vascular adaptations to myocardial hypertrophy. Annu. Rev. Physiol., 49, 477-487.
7) Bache R. J. (1988) : Effects of hypertrophy on the coronary circulation. Prog. Cardiovasc. Dis., 30, 403-440, 1988.
8) Haneda, T., Ichihara, K., Abiko, Y. and S. Onodera, (1986) : Functional and metabolic responses to ischemia in the perfused heart isolated from nor-motensive and spontaneously hypertensive rats. Jpn. Circ. J., 50, 607-611.
9) Mercadier, J. J., Lompre, A.-M., Duc, P., Boheler, K. R., Fraysse J.-B., Wisnewsky, C., Allen, P. D., Komajda, M. and K. Schwarts (1990) : Altered sarcoplasmic reticulum Ca²⁺-ATPase gene expression in the human ventricle during end-stage heart failure. J. Clin. Invest., 85, 305-309.
10) Cutilletta, A. F., Dowell, R. T., Rudnik, M., Arcilla, R. A. and R. Zak (1975) : Regression of myocardial hypertrophy. I. Experimental model, changes in heart weight, nucleic acids and collagen. J. Mol. Cell. Cardiol., 7, 767-781.
11) Panidis, JP., Kotler, M. N., Ren, J. F., Minitz, G. S., Ross, J. and P. Kalman, (1984) : Development and regression of left ventricular hypertrophy. J. Am. Coll. Cardiol., 3, 1309-1320.
12) Isoyama, S., Ito, N., Kuroha, M. and T. Takishima (1989) : Complete reversibility of physiological coronary vascular abnormalities in hypertrophied hearts produced by pressure-overload in the rat. J. Clin. Invest., 84, 288-294.
13) Imamura, S., Takao, A. and R. Matsuoka (1996) : Regression speed of cardiac myosin heavy chain isozyme V3 in loaded right or left ventricle after relief of the load. Eur., J. Clin., Invest., 26, 240-246.
14) Simpson, P.(1985) : Stimulation of hypertrophy of cultured neonatal rat heart cells through an bladrenergic receptor and induction of beating through an a1-and b1-adrenergic receptor interaction. Circ. Res., 56, 884-894.
15) Henrich, C. J. and P. C. Simpson (1988) : Differential acute and chronic response of protein kinase in cultured neonatal rat heart myocytes to a 1-adrenergic and phorbolester stimulation. J. Mol Cell. Cardiol., 20, 1081-1085.
16) Haneda, T. and P. J. McDermott (1991) : Stimulation of ribosomal RNA synthesis during hypertrophic growth of cultured heart cells by phorbol ester. Mol. Cell. Biochem., 104, 169-177.
17) Xenophantos, X., Watson, P. A., Chua, B. H. L., Haneda, T. and H. E. Morgan (1989) : Increased cyclic AMP content accelerates protein synthesis in rat heart. Circ. Res., 65, 647-656.
18) Imamura, S., Kimura, M., Hiratsuka, E., Takao, A. and R. Matsuoka (1992) : Effect of caffeine on expression of cardiac myosin heavy chain gene in adult hypothyroid and fetal rats. Circ. Res., 71, 1031-1038.
19) Matsuoka, R., Uno, H., Tanaka., H., Kerr, C. S., Nakazawa, K. and b. Nadal-Ginard (1987) : Caffeine induces cardiac and other malformations in the rat. Am, J. Med. Genet., 3 (suppl), 433-443.
20) Miyata, S. and T. Haneda (1994) : Hypertrophic growth of cultured neonatal rat heart cells mediated by type1 angiotensin II receptor. Am. J. Physiol., 266, H2443-H2451.
21) Pennica, D., King., K. L., Shaw, K. J., Luis, E., Rullamas, J., Luoh, S. M., Darbonne, W. C., Knutzon, D. S., Yen, R., Chien, K. R., Baker, J. B.and W. I. Wood (1995) : Expression cloning of cardiotrophin-1, a cytokine that induces cardiac myocyte hypertrophy. Proc. Natl. Acad. Sci. USA, 92, 1142-1146.
22) Imamura, S., Matsuoka, R., Hiratsuka, E., Kimura, M., Nishikawa, T. and A. Takao (1990) : Local response to cardiac overload on myosin heavy chain gene expression and isozyme transition. Circ. Res., 66, 1067-1073.
23) Komuro, I. and Y. Yazaki (1993) : Control of cardiac gene expression by mechanical stress. Annu. Rev. Physiol., 55, 55-75.
24) Komuro, I., Katoh, Y., Kaida, T., Shibazaki, Y., Kurabayashi, M., Hoh, E., Takaku, F. and Y. Yazaki (1991) : Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes. Possible role of protein kinase C activation. J. Biol. Chem., 266, 1265-1268.
25) Sadoshima, J., Xu, Y., Slayter, H. S.and S. Izumo (1993) : Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell., 75, 977-984.
26) Richardson, P., McKenna, W., Bristow, M., Maisch, B., Mautner B, O'Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I and P. Nordet (1996) : Report of the 1995 world health organization/international society and federation of cardiology task force on the definition and classification of cardiomyopathies. Circulation, 93, 841-842.
27) Jarcho, J. A., McKenna, W., Pare, J. A., Solomon, S. D., Holcombe, R. F., Dickie, S., Levi, T., Donis-Keller, H., Seidman, J. G. and C. E. Seidman (1989) : Mapping a gene for familial hypertrophic cardiomyopathy to chromosome 14q1. New Engl. J. Med., 321, 1372-1378.
28) Geisterfer-Lowrance, A. A., Kass, S., Tanigawa, G., Vosberg, H. P., McKenna, W., Seidman, C. E.,and J. G. Seidman (1990) : A molecular basis for familial hypertrophic cardiomyopathy : A b cardiac myosin heavy chain gene missense mutation. Cell, 62, 999-1006.
29) Tanigawa, G., Jarcho, J. A., Kass, S., Solomon, S. D., Vosberg, H. P., Seidman, J. G. and C. E. Seidman (1990) : A molecular basis for familial hypertrophic cardiomyopathy : An a/b cardiac myosin heavy chain hybrid gene. Cell, 62, 991-998.
30) Arai, S., Matsuoka, R., Hirayama, K., Sakurai, H., Tamura, M., Ozawa, T., Kimura, M., Imamura, S., Furutani, Y., Joh-o, K., Kawana, M., Takao, A., Hosoda, S. and K. Momma (1995) : Missense mutation of the b-cardiac myosin heavy-chaingene in hypertrophic cardiomyopathy. Am. J. Med. Genet., 58, 267-276.
31) Thierfelder, L., MacRae, C., Watkins, H., Tomfo-hrde, J., Williams, M., McKenna, W., Bohm, K., Noeske, G., Schlepper, M., Bowcock, A., Vosberg, H.-P., Seidman, J. G. and C. Seidman (1993) : A familial hypertrophic cardiomyopathy locus maps to chromosome 15q2. Proc. Natl. Acad. Sci., U. S. A., 90, 6270-6274.
32) Watkins, H., MacRae, C., Thierfelder, L., Chou, Y. H., Frenneaux, M., McKenna, W., Seidman, J. G. and C. E. Seidman (1993) : A disease locus for familial hypertrophic cardiomyopathy maps to chromosome 1q3. Nature Genet., 32, 333-337.
33) Thierfelder, L., Watkins, H., MacRae, C., Lamas R., McKenna, W., Vosberg. H. P., Seidman. J. G., and C. E. Seidman (1990) : α-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy. A. disease of the sarcomere. Cell, 62, 991-998.
34) Watkins, H., Conner, D., Thierfelder, L., Jarcho, J. A., MacRae, C., McKenna, W. J., Maron, B. J., Seidman, J. G. and C. E. Seidman (1995) : Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nature Genet., 11, 434-437.
35) Bonne, G., Carrier, L., Bercovici, J., Cruaud, C., Richard, P., Hainque, B., Gautel, M., Labeit, S., James ,M., Beckmann, J., Weissenbach, J., Vosberg, H.-P., Fiszman, M., Komajda, M. and K. Schwartz (1995) : Cardiac myosin binding protein-C gene splice acceptor site mutation is associated with familial hypertrophic cardiomyopathy. Nature Genet., 11, 438-441.
36) Cuda, G., Fananapazir, L., Zhu, W. S., Sellers, J. R. and N. D. Epstein (1993) : Skeletal muscle expression and abnormal function of b-myosin in hypertrophic cardiomyopathy. J. Clin. Invest., 91, 2861-2865.
37) Lankford, EB., Epstein, N. D., Fananapazir, L. and H. L. Sweeney (1995) : Abnormal contractile properties of muscle fibers expressing b-myosin heavy chain gene mutations in patients with hypertrophic cardiomyopathy. J. Clin. Invest., 95, 1409-1414.
38) Fukushima, Y., Ohashi, H., Wakui, K., Nishida, T. and T. Oh-ishi (1992) : A rapid method for starting a culture for the establishment of Epstein-Barr virus-transformed human lymphoblastoid cell lines. Jpn. J. Human Genet., 37, 149-150.

Abstract

Cardiac hypertrophy is actually a compensatory mechanism in response to an increased load imposedd on the heart, and should, thus, be considered to be an adaptive and, essentially, favorable process. In the abcence of such compensation, the cardiac ventricles would be less able to respond adequately to any burden laid on the heart. However, hypertrophy is ultimately a major risk factor for cardiovascular disease, including coronary circulation abnormalities. Therefore, it is logical that an important goal of treatment is to control ventricular hypertrophy, but how effectively this can be done and whether the associated risk with ventricular hypertrophy is also brought under control is still a matter of discussion. In this review, to understand cardiac hypertrophy better from the aspect of molecular biology, the transition of myosin heavy chain isoforms which are among the most important contractile components, and signal trasduction pathways in cardiac myocytes to induce myocyte hypertrophy are summarized. In addition, a recent molecular approach to hypertrophic cardiomyopathy in human medicine is described.

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