REVERSAL OF MYOCARDIAL HYPERTROPHY IN HYPERTENSION

这个项目的目标是研究潜在的机制 心肌肥厚的发生和/或消退 高血压。我们实验室的研究表明， 心血管肥厚的发展和消退并不是 仅依赖于机械载荷，但似乎受 不同等级，即增加压力负荷、等级 心脏肾上腺素能系统及各种体液因素的影响。一个 收缩蛋白组成的根本缺陷 心肌的成分也已被证实。以上内容 观察结果使我们继续研究心肌 肥大，在生化、细胞和分子水平上， 目的如下：1)进一步确定心肌的特征 肌球蛋白和胶原，这两个功能上重要的成分 心肌；2)明确不同的调节作用 影响上述变化的因素；3)上述变化与 确定心肌功能方面的重要性 生化缺陷；以及4)进一步调查 β-肾上腺素能系统与衰老对心肌的影响 高血压时的肥大。上述实验预计将 阐明在治疗过程中发生的生化缺陷 肥大的发展，尤其是在它从 慢性肥厚到心力衰竭。对这一概念的理解 心肌蛋白质合成的基本机制 在肥大发展或消退期间关闭或打开 也是极其重要的。目前还不能确定 与肥大相关的表型转换被反映出来 在心肌收缩能力方面，同样重要的是启动 分子水平的分析，这些因素控制着 大鼠心肌肥厚模型中心脏基因的表达 高血压。生化变化的平行研究和 功能方面应该有助于理解 肥大消退是有益的，也是有害的。结果是 这项研究的预期与以下问题直接相关 人类的高血压和肥厚。如果调制β- 肾上腺素能系统已被证明在增强 对于肥大，需要重新评估治疗方式。

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.