Molecular Mechanism of Cardiovascular Remodeling

Abstract

Angiotensinogen mRNA expression in human tissues was detected not only in the liver, but also in both atrial and ventricular heart tissues, suggesting that angiotensinogen is synthesized in the human heart. Angiotensinogen was present in the endocardial layer of the human left ventricle, rather than in the epicardial layer, and in the conduction system and right atrium. Furthermore, we found angiotensinogen to be widespread in the left ventricle of diseased hearts. We examined the involvement of collagen in the occurrence and progression of cardiomyopathy. In the early phase of cardiomyopathy, the extracellular matrix of the myocardium is rich in type III collagen, which is similar to immature tissues. In the later phase, the matrix resembles that of hard tissues in which collagen is mainly of type I and is insoluble. We also examined the relationship between angiotensin II and collagen synthesis. Previous studies have demonstrated that myocardial fibrosis accounts for impaired myocardial stiffness and ventricular dysfunction in hypertensive cardiac hypertrophy. Basal collagen synthesis in cardiac fibroblasts from spontaneously hypertensive rats (SHR) was 1.6 fold greater than that in Wistar-Kyoto rats. The responsiveness of collagen production to angiotensin II was significantly enhanced in SHR. This effect was angiotensin receptor specific because it was blocked by the competitive inhibitor. These results indicate angiotensin II may play an important role in collagen accumulation in hypertensive cardiac hypertrophy.