Heart failure, a major cause of morbidity and mortality in patients with pulmonary arterial hypertension (PAH), is an outcome of complex biochemical processes. In this study, we determined changes in microRNAs (miRs) in the right and left ventricles of normal and PAH rats. Using an unbiased quantitative miR microarray analysis we found: 1) miR-21-5p, -31-5 and 3p,-140-5 and 3p, -208b-3p, -221-3p, -222-3p, -702-3p, and -1298 were upregulated (>2-fold; P<0.05) in the right ventricle (RV) of PAH compared to normal rats, ; 2) miR-31-5 and 3p, and -208b-3p were upregulated (>2-fold; P<0.05) in the left ventricle plus septum (LV+S) of PAH compared to normal rats; 3) miR-187-5p, -208a-3p, and -877 were downregulated (>2-fold; P<0.05) in the RV of PAH compared to normal rats; and 4) no miRs were up- or downregulated with >2-fold in LV+S compared to RV of PAH and normal. Upregulation of miR-140 and miR-31 in the hypertrophic RV was further confirmed by QPCR. Interestingly, in comparison to control rats, expression of mitofusin-1 (MFN1), a mitochondrial fusion protein that regulates apoptosis, and which is a direct target of miR-140, was reduced in the RV relative to LV+S of PAH rats. We found a correlation between increased miR-140 and decreased MFN1 expression in the hypertrophic RV. Our results also demonstrated that upregulation of miR-140 and downregulation of MFN1 correlated with increased RV systolic pressure and hypertrophy. These results suggest that miR-140 and MFN1 play a role in the pathogenesis of PAH-associated RV dysfunction.
- heart failure
- pulmonary hypertension
- Copyright © 2016, American Journal of Physiology - Heart and Circulatory Physiology