Control of stress-dependent cardiac growth and gene expression by a microRNA

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 alpha-myosin heavy chain (alpha MHC) and up-regulation of beta MHC, the primary contractile proteins of the heart. We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the alpha MHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of beta MHC in response to stress and hypothyroidism. Thus, the alpha 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.