miR-133a Enhances the Protective Capacity of Cardiac Progenitors Cells after Myocardial Infarction

Abstract

SummarymiR-133a and miR-1 are known as muscle-specific microRNAs that are involved in cardiac development and pathophysiology. We have shown that both miR-1 and miR-133a are early and progressively upregulated during in vitro cardiac differentiation of adult cardiac progenitor cells (CPCs), but only miR-133a expression was enhanced under in vitro oxidative stress. miR-1 was demonstrated to favor differentiation of CPCs, whereas miR-133a overexpression protected CPCs against cell death, targeting, among others, the proapoptotic genes Bim and Bmf. miR-133a-CPCs clearly improved cardiac function in a rat myocardial infarction model by reducing fibrosis and hypertrophy and increasing vascularization and cardiomyocyte proliferation. The beneficial effects of miR-133a-CPCs seem to correlate with the upregulated expression of several relevant paracrine factors and the plausible cooperative secretion of miR-133a via exosomal transport. Finally, an in vitro heart muscle model confirmed the antiapoptotic effects of miR-133a-CPCs, favoring the structuration and contractile functionality of the artificial tissue.

Empowering Adult Stem Cells for Myocardial Regeneration V2.0

“…Other microRNAs recently identified in the CPC secretome under hypoxic conditions include: miR-292, mR-210, miR-103, miR-17, miR-199a, miR-20a and miR-15b [150]; microRNA exosomes generated after twelve hours under hypoxic conditions and injected demonstrate improved fractional shortening and reduced fibrosis in an adult rat ischemia / reperfusion model [150]. Likewise, microRNA 133a improves cardiac function through reduction of fibrosis and hypertrophy as well as increasing vascularization and cardiomyocyte proliferation in a rat myocardial infarction model [151]. Despite this relatively recent flurry of excitement regarding exosome-mediated effects, the mechanistic basis remains poorly understood and the long-term benefits in terms of restoring myocardial structure and function remain to be assessed.…”

Β-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells

“…Since microRNAs have been described to play a role in cardiac pathological fibrosis3536373839,cardiomyocyte proliferation, progenitors commitment and differentiation40414243, TGF-β-mediated epithelial-to-mesenchymal transition44, and to correlate with CDCs therapeutic potential4546, we selected a panel of miRNA genes to be analyzed in BB and NBB-CDCs20. Preference was given to those miRNAs showing altered expression due to β-blocking agents observed in other systems6747484950.…”

“…The expression of miR-1 can enhance embryonic stem cells differentiation into cardiomyocytes59, and was also shown to be upregulated upon induction of cardiac differentiation of human cardiac progenitors isolated from fetal heart42. MiR-133a has been shown to exert a protective anti-apoptotic effect on cardiomyocytes exposed to oxidative stress, and transplantation of miR-133a-overexpressing CDCs promoted increased functional recovery in a murine MI model43. Moreover, cardioprotective miR-133a expression can be induced in vitro by β-blocker carvedilol treatment48.…”

Effect of microRNA-208a on mitochondrial apoptosis of cardiomyocytes of neonatal rats

“…In addition, miRNA may also become the important biological marker for the myocardial injury, which would greatly contribute to the early diagnosis and prevention of acute myocardial infarction [18,19] . Lawrie et al found the miRNA in the human serum in 2008 [20] .…”