Control of Stress-Dependent Cardiac Growth and Gene Expression by a MicroRNA

Abstract

The heart responds to diverse forms of stress by hypertrophic growth accompanied by fibrosis and eventual diminution of contractility, which results from down-regulation of α–myosin heavy chain (αMHC) and up-regulation of βMHC, the primary contractile proteins of the heart. We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the α MHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of β MHC in response to stress and hypothyroidism. Thus, the α MHC gene, in addition to encoding a major cardiac contractile protein, regulates cardiac growth and gene expression in response to stress and hormonal signaling through miR-208.