Study on the Mechanism of circRNA-0024103 Reducing Endothelial Cell Injury by Regulating miR-363/MMP-10.

Cardiovascular diseases could damage the heart and blood vessels, which cause mortality and morbidity. It is of great significance to explore targeted therapeutic approaches for atherosclerosis that is one of the most common vascular lesions and the main pathological basis of cardiovascular disease. However, the function of circRNA-0024103 in cardiovascular diseases is still not clear. Therefore, we aim to observe the effect of circRNA-0024103 modulation of miR-363/MMP-10 axis on biological behaviors such as proliferation and migration of endothelial cells after ox-LDL induction. The effects on the proliferation ability of endothelial cells were observed by CCK-8 assay and EdU assay based on overexpression of circRNA-0024103 in combination with miR-363 mimic or MMP-10 siRNA, and then, the effects on apoptosis were detected by flow cytometry analysis. The effects on cell migration, invasion, and angiogenesis were further examined by scratch assay, transwell assay, and tube formation assay. The results in CCK-8 and EdU assays showed that miR-363 mimic or MMP-10siRNA significantly attenuated the proliferation-promoting effect of overexpressed circRNA-0024103 on cell proliferation. In flow cytometry assays to detect apoptosis, overexpression of circRNA-0024103 inhibited apoptosis of endothelial cells, and the intervention of combined miR-363 mimic or MMP-10 siRNA counteracted the inhibitory effect of overexpression of circRNA-0024103 on apoptosis, resulting in a significant increase in the number of endothelial cells undergoing apoptosis. The migration, invasion, and tube-forming ability of endothelial cells were significantly enhanced when circRNA-0024103 was overexpressed, while the promotion of migration, invasion, and the tube-forming ability by overexpression of circRNA-0024103 alone was counteracted when combined with miR-363 mimic or MMP-10 siRNA. circRNA-0024103 regulates the biological behaviors of endothelial cells such as proliferation, apoptosis, migration, and invasion through the miR-363/MMP-10 axis. Our finding provides a new therapeutic target for the treatment of atherosclerosis.

MALAT1 regulates hypertrophy of cardiomyocytes by modulating the miR-181a/HMGB2 pathway.

Noncoding RNAs are important for regulation of cardiac hypertrophy. The function of MALAT1 (a long noncoding mRNA), miR-181a, and HMGB2; their contribution to cardiac hypertrophy; and the regulatory relationship between them during this process remain unknown. In the present study, we treated primary cardiomyocytes with angiotensin II (Ang II) to mimic cardiac hypertrophy. MALAT1 expression was significantly downregulated in Ang II-treated cardiomyocytes compared with control cardiomyocytes. Ang II-induced cardiac hypertrophy was suppressed by overexpression of MALAT1 and promoted by genetic knockdown of MALAT1. A dual-luciferase reporter assay demonstrated that MALAT1 acted as a sponge for miR-181a and inhibited its expression during cardiac hypertrophy. Cardiac hypertrophy was suppressed by overexpression of a miR-181a inhibitor and enhanced by overexpression of a miR-181a mimic. HMGB2 was downregulated during cardiac hypertrophy and was identified as a target of miR-181a by bioinformatics analysis and a dual-luciferase reporter assay. miR-181a overexpression decreased the mRNA and protein levels of HMGB2. Rescue experiments indicated that MALAT1 overexpression reversed the effect of miR-181a on HMGB2 expression. In summary, the results of the present study show that MALAT1 acts as a sponge for miR-181a and thereby regulates expression of HMGB2 and development of cardiac hypertrophy. The novel MALAT1/miR-181a/HMGB2 axis might play a crucial role in cardiac hypertrophy and serve as a new therapeutic target.

LncRNA SNHG12 downregulates RAGE to attenuate hypoxia-reoxygenation-induced apoptosis in H9c2 cells.

Ischemia-reperfusion (I/R) injury causes cardiac dysfunction through several mechanisms including the irregular expression of some long noncoding RNA. However, the role of SNHG12 in myocardial I/R injury remains unclear. Here, we found the increase of the SNHG12 level in hypoxia-reoxygenation (H/R)-injured-H9c2 cells. SNHG12 silencing enhanced the apoptosis of H/R-injured H9c2 cells, while SNHG12 overexpression relieved the cardiomyocyte apoptosis induced by H/R stimulation. Additionally, the suppression of SNHG12 significantly boosted the H/R-induced expression and the production of TNF-α, IL-6, and IL-1ß, as well as the activation of NF-κB, which were fully reversed after overexpression of SNHG12. Mechanistically, SNHG12 adversely regulated the production of receptor for advanced glycation end products (RAGE) in H/R-stimulated H9c2 cells. Antibody blocking of RAGE alleviated the apoptosis of H/R-injured H9c2 cells. Collectively, we have determined a valuable mechanism by which the high level of SNHG12 contributes to H9c2 cells against H/R injury through the reduction of RAGE expression.

Clinical efficacy and safety of percutaneous coronary intervention for acute myocardial infarction complicated with chronic renal insufficiency: A protocol of systematic review and meta-analysis.

BACKGROUND: The aim of this research is to further evaluate the efficacy and safety of percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) complicated with chronic renal insufficiency (CRI) by meta-analysis, to provide scientific and effective medical evidence for PCI in patients with AMI complicated with CRI, and to support the clinical application of PCI. METHODS: Electronic databases will be searched, including PubMed, Cochrane Library, Embase, CNKI, CBM, VIP, and Wanfang Data. Patients with AMI complicated by renal insufficiency treated with PCI will be included. The retrieval time is from inception to January 2019. The inclusion and exclusion criteria are formulated to search only the relevant literature. Endnote software management for literature will be adopted. The literature will be independently screened by 2 researchers. Excel 2016 will be applied to extract literature data with the "Research Information Registration Form." The final selected literature will be assessed for bias risk. Stata 12.0 software will be used for the meta-analysis. RESULTS: The systematic evaluation and meta-analysis will be carried out strictly in accordance with the requirements of the Cochrane System Evaluator Manual 5.3 on meta-analyses, which will provide a high-quality evaluation of the clinical efficacy and safety of PCI in patients with AMI and CRI. ETHICS AND DISSEMINATION: This study belongs to the category of systematic reviews, not clinical trials. Therefore, it does not require ethical approval. The results of this study will be published in influential international academic journals related to this topic. CONCLUSION: PCI is an effective and safe treatment for patients with AMI and CRI. This study will provide a definite evidence-based medical conclusion and provide a scientific basis for the clinical treatment of patients with AMI and CRI. PROSPERO REGISTRATION NUMBER: CRD42019131367.