microRNAs-mediated MMPs regulation: Novel mechanism for cardiovascular diseases

Abstract

Cardiac remodeling and its role in disease progression is a multimechanistic and complex process. Disruption of normal extracellular matrix homeostasis is the most important event responsible for cardiac remodeling, altering heart structure and function. Therefore, targeting extracellular matrix remodeling enzymes such as matrix metalloproteinases has received much interest in terms of developing novel therapeutics strategies. Recent findings of microRNAs (endogenous, non-coding, ~22 nucleotide small RNA) in the cardiac tissue as dynamic modifiers of disease pathogenesis have provided glimpses of undiscovered regulatory mechanisms underlying cardiovascular diseases. The implication of several microRNAs in targeting extracellular matrix components (microRNA-29: collagen, fibrillin, elastin) and matrix metalloproteinases (microRNA-21: MMP-2; microRNA-320: MMP-9) has been well documented. The combined strategy of manipulating extracellular matrix remodeling through targeting matrix metalloproteinases by microRNAs has produced encouraging results in preclinical studies. This chapter reviews the potential of microRNA as therapeutics tool for cardiovascular diseases through direct and indirect interactions with the matrix metalloproteinases.