REVERSAL OF MYOCARDIAL HYPERTROPHY IN HYPERTENSION

这个项目的目的是研究潜在的机制

The objective of this project is to study underlying mechanisms of development and/or regression of myocardial hypertrophy in hypertension. Research from our laboratory has demonstrated that the development and regression of cardiovascular hypertrophy is not dependent upon mechanical load alone, but seems to be modulated at various levels, namely, increased pressure load, level of cardioadrenergic system and effect of various humoral factors. A fundamental defect in the composition of contractile protein element of the myocardium has also been demonstrated. The above observations led us to continue our study on myocardial hypertrophy, on biochemical, cellular, and molecular level, with the following aims: 1) to characterize further the myocardial myosin and collagen, the 2 functionally important components of the myocardium; 2) define the roles of different modulatory factors on the above changes; 3) correlate the above changes to the functional aspect of the myocardium to define the importance of biochemical defects; and 4) further investigate the involvement of the beta-adrenergic system and the influence of aging on myocardial hypertrophy in hypertension. The above experiment is expected to elucidate the biochemical defects that take place during development of hypertrophy, especially during its transition from chronic hypertrophy to heart failure. An understanding of the basic mechanism for how the protein synthesis of the myocardium is turned off or on during development or regression of hypertrophy is also of utmost importance. It remains to be determined how the phenotypic transitions associated with hypertrophy are reflected in myocardial contractility, and it is also important to initiate analysis of the molecular level of factors, which control the expression of cardiac genes in models of cardiac hypertrophy in hypertension. A parallel study of the biochemical changes and functional aspects should help to understand whether or not regression of hypertrophy is beneficial or harmful. The results expected from this study are directly related to problems with human hypertension and hypertrophy. If modulation of beta- adrenergic system is proven to play a role in accentuating hypertrophy, reappraisal of the therapeutic modalities is needed.