Therapeutic potential of targeting microRNAs to regulate cardiac fibrosis: miR-433 a new fibrotic player

Jenny Y. Y. Ooi, Bianca C. Bernardo, Julie R. McMullen


In response to stress, the heart undergoes cardiac remodelling to compensate for the increase in workload, and if left untreated can progress to heart failure and death. One of the key processes associated with pathological remodelling is the excessive extracellular matrix production by cardiac fibroblasts (i.e., cardiac fibrosis). Cardiac fibrosis reduces cardiac compliance, making the heart stiff, and this contributes to cardiac dysfunction and ultimately heart failure (1). At present, there is no therapy for cardiac fibrosis. Since the discovery of microRNAs (miRNAs) about 20 years ago, they have attracted much attention from numerous fields of biology and medicine, and are considered potential therapeutic targets. MicroRNAs are small (22 nucleotides), highly conserved non-coding RNA molecules (initially considered “junk”) that can regulate gene expression by binding to the 3’ untranslated region of its target mRNA (2). Numerous miRNAs are aberrantly expressed in settings of cardiovascular disease, and small molecule drugs that can modulate the expression of miRNAs have shown success in preclinical studies in cardiac stress settings (3).