Molecular genetic approach to the pathophysiology of cardiovascular disease.

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.