The Roles of a Matricellular CCN Family Protein CCN5 in Cardiac Fibrosis of Heart Failure

Abstract

Cardiac fibrosis is a major player in cardiovascular disease, both as a contributor to the development of disease and a post-injury response that drives progression to heart failure. Despite the identification of many mechanisms responsible for cardiovascular fibrosis, such as angiotensin II, TGF-[Formula: see text] and endothelin-1, to date no treatments have emerged that have effectively reduced the excess deposition of extracellular matrix associated with fibrotic conditions. Matricellular CCN proteins spatiotemporally regulated nonstructural components of the extracellular matrix (ECM) and participated in many essential biological functions, including wound healing and fibrotic diseases. CCN5 exhibited the opposing effects of CCN2 on the development of cardiac hypertrophy and fibrosis, and overexpression of matricellular protein CCN5 in the heart by adenoviral deliver significantly improved cardiac fibrosis in severe heart failure. Future time- and cell-specific study of CCN5 effect and its domain-specific function on fibrotic development and progression will advance our understanding of cardiac fibrosis, and meanwhile provide opportunities for therapeutic intervention of heart failure.