Figure 3. Functional role of miRNAs in the normal and diseased heart.

A normal and a hypertrophic heart are shown in schematic form, depicting miRNAs that contribute to normal function or pathological remodelling. The expression of selected miRNAs within the heart is shown, along with their corresponding functions. All arrows denote the normal action of each component or process. miR-1 and miR-133 are involved in the development of a normal heart (left) by regulating proliferation, differentiation and cardiac conduction. For example, proliferation is promoted by cell-cycle regulators, but miR-1 and miR-133 block these regulators, thus blocking proliferation. miR-208a also contributes to the regulation of the conduction system. After cardiac injury (right), various miRNAs contribute to pathological remodelling and the progression to heart failure. miR-29 and miR-21 block and promote cardiac fibrosis, respectively. miR-29 blocks fibrosis by inhibiting the expression of ECM components, whereas miR-21 promotes fibrosis by stimulating mitogen-activated protein kinase (MAPK) signalling. miR-208 controls myosin isoform switching, cardiac hypertrophy and fibrosis. miR-23a promotes cardiac hypertrophy by inhibiting ubiquitin proteolysis, which itself inhibits hypertrophy. Hypoxia results in the repression of miR-320 and miR-199, which promote and block apoptosis, respectively. ECM, extracellular matrix; LV, left ventricle; MHC, myosin heavy chain; RV, right ventricle.