Exercise training in spontaneously hypertensive rats reduced miRNA-16 and -21 levels and elevated vascular endothelial growth factor and Bcl-2 levels, promoting peripheral revascularization.
Does aerobic exercise training improve microvascular rarefaction and modulate angiogenic miRNAs in a rat model of hypertension?
Aerobic exercise training promotes peripheral revascularization in hypertension by modulating specific miRNAs (miRNA-16, -21, -126) and balancing angiogenic and apoptotic factors.
Aerobic exercise training (ET) lowers hypertension and improves patient outcomes in cardiovascular disease. The mechanisms of these effects are largely unknown. We hypothesized that ET modulates microRNAs (miRNAs) involved in vascularization. miRNA-16 regulates the expression of vascular endothelial growth factor and antiapoptotic protein Bcl-2. miRNA-21 targets Bcl-2. miRNA-126 functions by repressing regulators of the vascular endothelial growth factor pathway. We investigated whether miRNA-16, -21 and -126 are modulated in hypertension and by ET. Twelve-week-old male spontaneously hypertensive rats (SHRs; n=14) and Wistar Kyoto (WKY; n=14) rats were assigned to 4 groups: SHRs, trained SHRs (SHR-T), Wistar Kyoto rats, and trained Wistar Kyoto rats. ET consisted of 10 weeks of swimming. ET reduced blood pressure and heart rate in SHR-Ts. ET repaired the slow-to-fast fiber type transition in soleus muscle and the capillary rarefaction in SHR-Ts. Soleus miRNA-16 and -21 levels increased in SHRs paralleled with a decrease of 48% and 25% in vascular endothelial growth factor and Bcl-2 protein levels, respectively. Hypertension increased Bad and decreased Bcl-x and endothelial NO synthase levels and lowered p-Bad(ser112):Bad ratio. ET in SHR-Ts reduced miRNA-16 and -21 levels and elevated vascular endothelial growth factor and Bcl-2 levels. ET restored soleus endothelial NO synthase levels plus proapoptotic and antiapoptotic mediators in SHR-Ts, indicating that the balance between angiogenic and apoptotic factors may prevent microvascular abnormalities in hypertension. miRNA-126 levels were reduced in SHRs with an increase of 51% in phosphoinositol-3 kinase regulatory subunit 2 expression but normalized in SHR-Ts. Our data show that ET promoted peripheral revascularization in hypertension, which could be associated with regulation of select miRNAs, suggesting a mechanism for its potential therapeutic application in vascular diseases.
Fernandes et al. (Wed,) conducted a other in Hypertension (n=28). Exercise training vs. No exercise training was evaluated on miRNA-16, -21 and -126 levels, vascular endothelial growth factor, and Bcl-2 protein levels. Exercise training in spontaneously hypertensive rats reduced miRNA-16 and -21 levels and elevated vascular endothelial growth factor and Bcl-2 levels, promoting peripheral revascularization.