Abstract

The goal of this chapter is to discuss the regulation of cardiac fibrosis by miRNAs. Cardiac myocytes are normally surrounded by a fine network of collagen fibers. In the normal heart, two thirds of the cell population is composed of nonmuscle cells, the majority of which are fibroblasts. Cardiac fibrosis is the result of both an increase in fibroblast proliferation and extracellular matrix (ECM) deposition. A growing body of evidence indicates that, along with cardiomyocytes hypertrophy, diffusion of interstitial fibrosis is a key pathologic feature of myocardial remodelling in a number of cardiac diseases of different (e.g. ischemic, hypertensive, valvular, genetic, and metabolic) origin. The extracellular matrix (ECM) is a dynamic microenvironment; changes within ECM constitute the second important myocardial adaptation that occurs during cardiac remodelling. A subset of miRNAs is enriched in cardiac fibroblasts compared to cardiomyocytes. A number of studies have demonstrated the involvement of miRNAs in regulating myocardial fibrosis in the settings of myocardial ischemia or mechanical overload. Some miRNAs (miR-208 and miR-21) have been shown to favor fibrogenesis, being profibrotic miRNAs. Others including miR-29, miR-133, miR-30c, and miR-590 have been demonstrated to produce inhibitory effects on fibrogenesis, being anti-fibrotic miRNAs.