Mir-33: miR-acles in cardiac fibrosis?

Heart diseases (HDs) are the primary cause of death in the world (1). An estimated 17.3 million people died from HDs in 2015 (1), representing about 30% of all global deaths. Heart failure is the clinical manifestation of numerous forms of HDs. It is a destructive disorder characterized by ventricular remodeling and reduced compliance. In nearly all etiologies of HDs, the progression toward failure is accelerated by fibrosis, i.e., the improper deposition of extracellular matrix (ECM) proteins by cardiac fibroblasts (CFs) resulting in the reduction of tissue compliance. Physiologically, fibroblasts are the major cell type implicated in the construction and maintenance of connective tissue. The ECM, a highly organized collagen­rich meshwork, provides a structural and flexible scaffold for cardiac cells populations, dispenses mechanical forces through the myocardium, and mediates mechanical conduction of cells in the environment (2-4). CFs are fundamentally involved into the heart response to injury and tackle the limited regenerative capacity of the heart after injury. Fibrotic scar tissues preserve cardiac tissue structure and function. Upon injury, CFs within the connective tissue are activated, and secrete high levels of ECM to generate a pro-fibrotic environment. This environment enhances stiffness of the cardiac tissue and inhibits ventricular contraction and relaxation, which lead to abnormal heart architecture and function. Excessive ECM deposition and fibrosis have been clearly associated with myocardial diastolic and systolic dysfunctions (5). Inhibiting or reversing fibrosis and its damaging repercussions is an established strategy used in many clinical interventions aiming to treat HDs.