| First Author | Huang ZP | Year | 2013 |
| Journal | Circ Res | Volume | 112 |
| Issue | 9 | Pages | 1234-43 |
| PubMed ID | 23524588 | Mgi Jnum | J:213308 |
| Mgi Id | MGI:5584072 | Doi | 10.1161/CIRCRESAHA.112.300682 |
| Citation | Huang ZP, et al. (2013) MicroRNA-22 regulates cardiac hypertrophy and remodeling in response to stress. Circ Res 112(9):1234-43 |
| abstractText | RATIONALE: The adult heart is composed primarily of terminally differentiated, mature cardiomyocytes that express signature genes related to contraction. In response to mechanical or pathological stress, the heart undergoes hypertrophic growth, a process defined as an increase in cardiomyocyte cell size without an increase in cell number. However, the molecular mechanism of cardiac hypertrophy is not fully understood. OBJECTIVE: To identify and characterize microRNAs that regulate cardiac hypertrophy and remodeling. METHODS AND RESULTS: Screening for muscle-expressed microRNAs that are dynamically regulated during muscle differentiation and hypertrophy identified microRNA-22 (miR-22) as a cardiac- and skeletal muscle-enriched microRNA that is upregulated during myocyte differentiation and cardiomyocyte hypertrophy. Overexpression of miR-22 was sufficient to induce cardiomyocyte hypertrophy. We generated mouse models with global and cardiac-specific miR-22 deletion, and we found that cardiac miR-22 was essential for hypertrophic cardiac growth in response to stress. miR-22-null hearts blunted cardiac hypertrophy and cardiac remodeling in response to 2 independent stressors: isoproterenol infusion and an activated calcineurin transgene. Loss of miR-22 sensitized mice to the development of dilated cardiomyopathy under stress conditions. We identified Sirt1 and Hdac4 as miR-22 targets in the heart. CONCLUSIONS: Our studies uncover miR-22 as a critical regulator of cardiomyocyte hypertrophy and cardiac remodeling. |
