Kurabayashi M, Yazaki Y
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo.
Int Angiol. 1996 Sep;15(3):187-94.
The delineation of the molecular mechanisms of cardiovascular disease is an important initial step in developing improved methods of screening and therapy. Recently, progress has been made in characterizing the molecular basis of several inherited cardiovascular diseases, particularly as to the diseases caused by defects in single gene. When the disease under study has a complex etiology with multiple genetic and environmental components, it becomes much more difficult to dissect out the genetic factors and to distinguish between causation and correlation. Gene targeting in mice provides a means to test the effect of a precise genetic change completely free from the effects of differences in any other genes. Models of several human genetic diseases have been produced by gene targeting and the resulting "knockout" mice have often confirmed that the disease is the consequence of the defect of a gene of interest. The review will focus on the how molecular genetic approach is useful to understand the basic mechanism of complex genetic diseases, including essential hypertension, atherosclerosis, congenital heart disease. Particular emphasis will be given to the renin angiotensin system because a large body of evidence indicates its greater role in the pathogenesis of many complex cardiovascular diseases than has been recognized.
阐明心血管疾病的分子机制是开发改进的筛查和治疗方法的重要第一步。最近，在确定几种遗传性心血管疾病的分子基础方面取得了进展，特别是对于由单基因缺陷引起的疾病。当所研究的疾病具有复杂的病因，涉及多种遗传和环境因素时，剖析遗传因素并区分因果关系和相关性就变得更加困难。小鼠基因靶向技术提供了一种方法，可以测试精确基因变化的效果，完全不受任何其他基因差异的影响。通过基因靶向产生了几种人类遗传疾病的模型，由此产生的“基因敲除”小鼠常常证实该疾病是所关注基因缺陷的结果。本综述将重点关注分子遗传学方法如何有助于理解复杂遗传疾病的基本机制，包括原发性高血压、动脉粥样硬化、先天性心脏病。将特别强调肾素 - 血管紧张素系统，因为大量证据表明它在许多复杂心血管疾病的发病机制中所起的作用比人们所认识到的更大。
