MicroRNAs (miRNA) are short nucleotide chains that act as inhibitors of gene expression. Specifically, miR-499 is a cardiac-abundant microRNA that can prevent cardiomyocyte apoptosis by targeting calcineurin-mediated activation of Drp1, an enzyme that normally results in fission of mitochondrial tubules into fragments. miR-499 may therefore have a key role to play following myocardial infarction, as abnormal mitochondrial fission is involved in the initiation of apoptosis.
Wang and colleagues found that inhibition of miR-499 was associated with larger infarct size and decreased cardiac function following a period of ischaemia-reperfusion in a mouse model. Subsequently,inhibition of miR-499 was also seen to aggravate deleterious cardiac remodeling after ischemia-reperfusion, as revealed by increased collagen deposition and cardiomyocyte hypertrophy, and also by enlarged cardiac chamber dimensions and more pronounced cardiac dysfunction. The authors also noted that p53 seemed to participate in the regulation of miR-499, as knockdown of p53 in hearts subjected to ischemia-reperfusion in vivo attenuated the reduction in miR-499 levels seen.
These data reveal a role for miR-499 in regulating mitochondrial fission and suggest that modulation of miR-499 levels may provide a therapeutic target for treating myocardial infarction in the future.
- Wang J-X, Jiao J-Q, Li Q et al. miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1. Nature Medicine; published online 26 December 2010; doi:10.1038/nm.2282