Post myocardial infarction (MI) fibrosis has been identified as an important factor in the progression of heart failure. Previous studies have revealed that microRNA-21 (miR-21) plays an important role in the pathogenesis of fibrosis. The purpose of this study was to explore the role of miR-21 in post-MI cardiac fibrosis. Material and Methods: MI was established in wild-type (WT) and miR-21 knockout (KO) mice. Primary mice cardiac fibroblasts (CFs) were isolated from WT and miR-21 KO mice and were treated with angiotensin II (Ang II) or Sprouty1 (Spry1) siRNA. Histological analysis and echocardiography were used to determine the extent of fibrosis and cardiac function. Results: Compared with WT mice, miR-21 KO mice displayed smaller fibrotic areas and decreased expression of fibrotic markers and inflammatory cytokines. In parallel, Ang IIinduced myofibroblasts transformation was partially inhibited upon miR-21 KO in primary CFs. Mechanistically, we found that the expression of Spry1, a previously reported target of miR-21, was markedly increased in miR-21 KO mice post MI, further inhibiting ERK1/2 activation. In vitro studies showed that Ang II activated ERK1/2/TGF-β/Smad2/3 pathway. Phosphorylated Smad2/3 further enhanced the expression of α-SMA and FAP and may promote the maturation of miR-21, thereby downregulating Spry1. Additionally, these effects of miR-21 KO on fibrosis were reversed by siRNA-mediated knockdown of Spry1. Conclusion: Our findings suggest that miR-21 promotes post-MI fibrosis by targeting Spry1. Furthermore, it mediates a positive feedback on Ang II, thereby inducing the ERK/ TGF-β/Smad pathway. Therefore, targeting the miR-21-Spry1 axis may be a promising therapeutic option for ameliorating post-MI cardiac fibrosis.

Background. The purpose of this study was to evaluate the association between the non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio and the risk of coronary artery disease (CAD). We also explored the potential role of non-HDL-C/HDL-C in the prognosis of CAD. Methods. We analyzed 930 consecutive patients with chest discomfort who underwent coronary angiography. Of these, 680 were diagnosed with CAD; the remaining 250 patients were normal. Multivariate logistic regression and receiver operating characteristic (ROC) curves were employed to evaluate the association between non-HDL-C/HDL-C and CAD. The effect of non-HDL-C/HDL-C on the progression of major adverse cardiovascular events (MACEs) was also explored. Results. Increased non-HDL-C/HDL-C was associated with an increased risk of CAD (OR: 1.291; 95% CI: 1.039-1.561; P=0.013). The results of stratified analyses by CAD subtype showed a correlation between high non-HDL-C/HDL-C and increased risk of acute coronary syndrome (OR: 1.661; 95% CI: 1.259-2.207; P<0.001), high Gensini score (OR: 1.408; 95% CI: 1.021-1.935; P=0.039), and multivessel disease (OR: 1.487; 95% CI: 1.128-1.992; P=0.007). Moreover, the areas under the ROC for the predictive value of non-HDL-C/HDL-C for CAD, acute coronary syndrome, high Gensini score, and multivessel disease were 0.604, 0.658, 0.642, and 0.636, respectively. Non-HDL-C/HDL-C in CAD patients was significantly correlated with the risk of long-term MACEs (P=0.004). Conclusions. The findings of this study indicated that non-HDL-C/HDL-C plays an important role in the risk and progression of CAD. These findings need verification by further large-scale prospective studies.

Objective Cardiomyocyte apoptosis critically contributes to ischemia reperfusion injury (IRI), which lacks effective therapeutic strategies. Circular RNAs (circRNAs) serve as novel diagnostic and therapeutic targets in various cardiovascular diseases. CircRNA Fbxl5 is one of the abundantly expressed circRNAs in the heart and its role in myocardial IRI remains elusive. Materials and Methods Wild-type (WT) mice and neonatal mice ventricular myocytes (NMVMs) were used and subjected to myocardial IRI and anoxia reoxygenation (AR), respectively. Molecular and histological analyses and echocardiography were used to determine the extent of apoptosis, infarct size, and cardiac function. Results We found that circRNA Fbxl5 was significantly upregulated in the myocardium, as well as in NMVMs subjected to AR. Knockdown of circRNA Fbxl5 ameliorated cardiomyocyte apoptosis, thereby decreasing infarct size and preserving cardiac function. Additionally, in vitro knockdown of circRNA Fbxl5 in NMVMs subjected to AR recapitulated the in vivo findings. Mechanistically, we identified that circRNA Fbxl5 directly sponged and suppressed the endogenous microRNA-146a (miR-146a), thereby weakening its inhibitory effect on MED1, which could further promote the apoptosis of cardiomyocytes. Conclusion Our findings revealed a novel and critical role for circRNA Fbxl5 in regulating cardiomyocyte apoptosis, and added additional insight into circRNAs mediated during myocardial IRI. The underlying miR-146a-MED1 signaling serves as an important cascade in regulating the apoptosis of cardiomyocytes.