Although the physiological properties of the myocardium and their dynamic character have been the focus of intense research during the past three decades, the biochemical and molecular correlates underlying cardiac development and performance have, until recently, remained poorly understood. The development of modern cellular and molecular biology has provided the necessary tools to undertake the study of the mechanisms involved in cardiac development and to understand the basis for important clinical and experimental problems in cardiovascular physiology. Most of the gene encoding contractile proteins have been cloned and characterized.The availability of molecular probes and the ability to introduce genes into individual cell types and tissues of living animals, are the most important breakthroughs of molecular and cell biology This permits not only to analyze basic mechanisms of gene expression but has also significant practical applications for gene therapy. It is now possible to analyze the role of different regulatory gene sequences and identify their corresponding trans-active factors. In addition, direct gene injection makes it possible to study gene expression in a natural context, under conditions that are physiologically relevant and controlable.
Key wordGene regulation α-, β-myosin heavy chain transcription factors cardiac development and hypertrophy thyroid hormones in vitro and in vivo gene transfer
Unable to display preview. Download preview PDF.
- 2.Barany M (1967) ATPase activity of myosin correlated with speed of muscle shortening. J Gen Physiol 50:suppl: 197–218Google Scholar
- 6.Endo T, Nadal-Ginard B (1989) Sv 40 large T-antigen induces re-entry of terminally differentiated myotubes into the cell cycle. In Kedes LH, Stockdale FE (ed) Cellular and Molecular Biology of Muscle Development, UCLA Symposia on Molecular and Cellular Biology New Series vol 93; AR Liss New York, p 95–104Google Scholar
- 12.Izumo S, Lompre A-M, Matsuoka R, Koren G, Schwartz K, Nadal-Ginard B, Mahdavi V (1987) Myosin heavy chain messenger RNA and protein isoform transitions during cardiac hypertrophy: Interaction between hemodynamic and thryroid hormone-induced signals. J Clin Invest 79: 970–977Google Scholar
- 18.Mahdavi V, Koren G, Michaud S, Pinset C, Izumo S (1989) Identification of the sequences responsible for the tissue-specific and hormonal regulation of the cardiac myosin heavy chain genes. In: Kedes LH, Stockdale FE (ed) Cellular and Molecular Biology of Muscle Development, UCLA Symposia on Molecular and Cellular Biology New Series vol 93; AR Liss New York, pp 369–379Google Scholar
- 20.O’Brien TX, Hunter JJ, Dyson E, Chien KR (1991) Heart-to-Heart, new approaches for gene transfer in the myocardium. Circulation 86: 2133–2136Google Scholar
- 25.Thompson WR, Koren G, Izumo S, Mahdavi V, Nadal-Ginard B (1990) Molecular regulation of myosin heavy chain switches: A model for study of cardiac gene expression. In: Clark EB and Takao A (ed) Developmental Cardiology: Morphogenesis and Function; Mount Kisko NY pp 13–25Google Scholar
- 26.Thompson WR, Mahdavi V, Nadal-Ginard B (1992) A MyoDl-independent muscle-specific enhancer controls the expression of the beta-myosin heavy chain gene in skeletal and cardiac muscle cells. J Biol Chem 266: 22678–22688Google Scholar
- 27.von Harsdorf R, Schott RJ, Shen Y-T, Vatner SF, Mahdavi V, Nadal-Ginard B (1993) Gene injection onto canine myocardium as a useful model for studying gene expression in the heart of large mammals. Circ Res 72: 688–695Google Scholar
- 32.Zak R (1974) Development and proliferative capacity of cardiac muscle cells. Circ Res 35:suppl 11: 17–26Google Scholar