Downregulation of microRNA-17-5p improves cardiac function after myocardial infarction via attenuation of apoptosis in endothelial cells

Abstract

MicroRNA-17-5p (miR-17-5p) was indicated to suppress the formation of blood vessels, which is associated with cardiac function after myocardial infarction. In this study, the relationship between miR-17-5p and cardiac function was researched. Human umbilical vein endothelial cells were infected with adenoviruses. Apoptosis was determined by Annexin V-7AAD/PI. Real-time RT-PCR was used to evaluate miR-17-5p and ERK levels. Western blotting was used to determine the levels of ERK, the anti-apoptosis protein bcl-2 and apoptosis proteins, including bax, caspase 3, and caspase 9. An in vivo acute myocardial infarction (AMI) model was established in SD male rats. Heart function was evaluated by echocardiography prior to inducing AMI and after 7 and 28 days later. The heart was removed to perform histological examination, real-time RT-PCR, and western blotting, as described above. The result indicated that the ERK pathway was activated by miR-17-5p downregulation and an increase in the level of the anti-apoptosis protein bcl-2; however, the levels of apoptosis proteins (bax/caspase 3/caspase 9) were decreased. The results were completely reversed when miR-17-5p was up-regulated. At 7 and 28 days after the induction of AMI, in the miR-17-5p inhibition group, the infarction areas and collagen fibers were decreased, apoptosis in cardiac tissues was inhibited, and the endothelial growth process was promoted. Therefore, MiR-17-5p silencing protects heart function after AMI through decreasing the rate of apoptosis and repairing vascular injury.

Downregulated expression of microRNAs associated with cardiac hypertrophy and fibrosis in physiological pregnancy and the association with echocardiographically‑evaluated myocardial function

“…Higher expression levels of miR-17-5p were observed to be associated with improved relaxation, as shown by higher values of the E to A wave ratio and lower estimated left ventricular filling pressures, shown by lower values of the E to E'med and E to E'lat ratios (see Table V for detailed results). Experimental mouse models of myocardial infarction demonstrated that knockdown of miR-17-5p expression decreased infarction area and the area of fibrosis and stimulated endothelial growth (25). Therefore, decreased expression of miR-17-5p may serve a regulatory role in diastolic function adaptation in pregnancy.…”

MicroRNAs and obesity-induced endothelial dysfunction: key paradigms in molecular therapy

“…The ATG system is required for the LC3 to conjugate to phosphotidylethanolamine (PE) phospholipids and to form LC3 II. LC3 II is important for the expansion of the membrane, where it plays a crucial role in cargo recognition via its interaction to [178,181] miR-199a Up [184,188] EC dysfunction [185] mTOR, ULK1 [178,180,182,185] miR-101 Up [186,188] EC dysfunction [187] mTOR [178,179] miR-451 Up [193] Cardiac hypertrophy [193] AMPK [193,195] miR-148b Up [194] Hyperglycemia-induced EC dysfunction [155] AMPK [192] miR-20a Up [143] Regulates EC migration, angiogenesis and senescence [203,211] ULK1, FIP200 [199,208] miR-20b Up [209] Promotes EC senescence [210,211] FIP200 [208] miR-106b Up [204] EC proliferation and atherosclerosis [205] ULK1 [199,201] miR-17-5p Up [206] ECs apoptosis and cardiac dysfunction [207] ULK1 [202] miR-506-3p Unknown -Aggravates injury in vascular EC [212] Beclin 1 [ [212] miR-216a Unknown -Controls ox-LDL induced autophagy [216] Beclin 1 [216] miR-129-5p Up…”

“…Likewise, miR-17-5p expression differs significantly between patients with and without obesity [ 206 ]. Downregulation of this miRNA improves cardiac function after a myocardial infarction through attenuation of EC apoptosis [ 207 ]. Altogether, these studies point toward the importance of the ULK1 in the cardiovascular system and more specifically endothelial function.…”

MicroRNA changes in maternal serum from pregnancies complicated by twin‐twin transfusion syndrome: A discovery study

“…62 A recent study has found that downregulation of hsa-miR-17-5p improves cardiac function after myocardial infarction, thought to be due to aiding repair of vascular injury, and decreasing the rate of apoptosis. 63 Other miRNAs that were significant prior to correction for multiple testing have also been demonstrated to be significantly different in maternal serum from singleton pregnancies complicated by preeclampsia:…”