Abstract Background: In-stent restenosis (ISR) is one of the most important complications and impacts the long-term effects after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). Related studies have revealed that microRNA (miRNA) can predict ISR in CHD patients. MiRNA-126 may be a potential biomarker for the diagnosis of ISR. However, the accuracy of miRNA-126 in the diagnosis of ISR is still controversial. Therefore, this study carried out meta-analysis to further evaluate the accuracy of miRNA-126 in the diagnosis of ISR. At the same time, bioinformatics is used to predict the target genes and miRNA-126 may be involved in regulation, so as to provide theoretical support for the precise treatment of CHD. Methods: The literatures on the miRNA-126 diagnosis of ISR in CHD patients were collected by searching on computer through China National Knowledge Infrastructure, Wanfang, China Biology Medicine disc, PubMed, EMBASE, Cochrane Library and Web of Science. The retrieval time is set to build the database until April 2021. The meta-analysis of the literatures that meet the quality standards was conducted by Stata 16.0 software. TargetScan database, PicTar database, miRanda database, and miRDB database were used to predict miRNA-126 intersection target genes. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analysis of miRNA-126 target genes were performed by using DAVID database. STRING database was applied to analyze the protein-protein interaction (PPI) network of miRNA-126 target genes. The “Networkanalyzer” function of Cytoscape3.7.2 software is adopted to analyze the network topology attributes, so as to find out the core genes of PPI network. Results: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. Conclusion: In this study, meta-analysis and bioinformatics analysis were adopted to further evaluate the accuracy of miRNA-126 in the diagnosis of ISR in CHD patients, and to explore the mechanism of the action of miRNA-126 and understand related pathways. Ethics and dissemination: The private information from individuals will not be published. This systematic review also should not damage participants’ rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/9FMR5.

Background: In-stent restenosis (ISR) is one of the most important complications and impacts the long-term effects after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). Related studies have revealed that microRNA (miRNA) can predict ISR in CHD patients. MiRNA-126 may be a potential biomarker for the diagnosis of ISR. However, the accuracy of miRNA-126 in the diagnosis of ISR is still controversial. Therefore, this study carried out meta-analysis to further evaluate the accuracy of miRNA-126 in the diagnosis of ISR. At the same time, bioinformatics is used to predict the target genes and miRNA-126 may be involved in regulation, so as to provide theoretical support for the precise treatment of CHD. Methods: The literatures on the miRNA-126 diagnosis of ISR in CHD patients were collected by searching on computer through China National Knowledge Infrastructure, Wanfang, China Biology Medicine disc, PubMed, EMBASE, Cochrane Library and Web of Science. The retrieval time is set to build the database until April 2021. The meta-analysis of the literatures that meet the quality standards was conducted by Stata 16.0 software. TargetScan database, PicTar database, miRanda database, and miRDB database were used to predict miRNA-126 intersection target genes. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analysis of miRNA-126 target genes were performed by using DAVID database. STRING database was applied to analyze the protein-protein interaction (PPI) network of miRNA-126 target genes. The "Networkanalyzer" function of Cytoscape3.7.2 software is adopted to analyze the network topology attributes, so as to find out the core genes of PPI network. Results: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. Conclusion: In this study, meta-analysis and bioinformatics analysis were adopted to further evaluate the accuracy of miRNA-126 in the diagnosis of ISR in CHD patients, and to explore the mechanism of the action of miRNA-126 and understand related pathways. Ethics and dissemination: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/9FMR5.

BACKGROUND:Arteriosclerosis has genetic correlation. Many studies have shown that angiotensin II type 1 receptor (AT1R) gene A1166C polymorphism is highly associated with arteriosclerosis, but there is no evidence-based basis. The purpose of this study is to systematically evaluate the relationship between AT1R gene A1166C polymorphism and arteriosclerosis.METHODS:The search time is set from the establishment of the database in December 2020 in this study. The search database include China National Knowledge Infrastructure (CNKI), Wanfang, VIP and China Biology Medicine disc (CBM), PubMed, EMBASE, Web of Science, and the Cochrane Library. The subjects are observational studies on the relationship between AGTR1 A1166C polymorphism and arteriosclerosis (including case-control study, cross-sectional study, and cohort study). The language is limited to English and Chinese. The data of the included study are extracted and the literature quality is evaluated by 2 researchers independently. The data are statistically analyzed by Stata 16.0 software.RESULTS:This study will use pulse wave velocity as an index to evaluate arteriosclerosis to explore the relationship between AT1R gene A1166C polymorphism and arteriosclerosis.CONCLUSION:This study will provide evidence-based medicine for elucidating the genetic tendency of arteriosclerosis.ETHICS AND DISSEMINATION:Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.OSF REGISTRATION NUMBER:DOI 10.17605/OSF.IO/V6E2Y.

Abstract Background: Evidence reveals that microRNA (miRNA) can predict coronary restenosis in patients suffering from coronary heart disease (CHD) after percutaneous coronary intervention (PCI). Perhaps, miRNA-21 is a promising biomarker for the diagnosis of coronary restenosis after PCI. However, the accuracy of miRNA-21 has not been systematically evaluated. Therefore, it is necessary to perform meta-analysis to certify the diagnostic values of miRNA-21 on coronary restenosis after PCI. Methods: China National Knowledge Infrastructure, Wanfang, VIP, and China Biology Medicine disc, PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant studies to explore the potential diagnostic values of miRNA-21 on coronary restenosis after PCI from inception to January 2021. All data were extracted by 2 experienced researchers independently. The risk of bias about the meta-analysis was confirmed by the Quality Assessment of Diagnostic Accuracy Studies-2. The data extracted were synthesized and heterogeneity was investigated as well. All of the above statistical analyses were carried out with Stata 16.0. Results: This study proved the pooled diagnostic performance of miRNA-21 on coronary restenosis after PCI. Conclusion: This study clarified confusions about the specificity and sensitivity of miRNA-21 on coronary restenosis after PCI, thus further guiding their promotion and application. Ethics and dissemination: Ethical approval is not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations. OSF Registration Number: DOI 10.17605/OSF.IO/356QK.

Obesity is often associated with increased risk of cardiovascular diseases. Previous studies suggest that epidermal growth factor receptor (EGFR) antagonism may be effective for the treatment of angiotensin II-induced cardiac hypertrophy and diabetic cardiomyopathy. This study was performed to demonstrate if EGFR plays a role in the pathogenesis of hyperlipidemia/obesity-related cardiac injuries. The in vivo studies using both wild type (WT) and apolipoprotein E (ApoE) knockout mice fed with high fat diet (HFD) showed the beneficial effects of small-molecule EGFR inhibitors, AG1478 and 542, against obesity-induced myocardial injury. Administration of AG1478 and 542 significantly reduced myocardial inflammation, fibrosis, apoptosis, and dysfunction in both two obese mouse models. In vitro, EGFR signaling was blocked by either siRNA silencing or small-molecule EGFR inhibitors in palmitic acid (PA)-stimulated cardiomyocytes. EGFR inhibition attenuated PA-induced inflammatory response and apoptosis in H9C2 cells. Furthermore, we found that PA-induced EGFR activation was mediated by the upstream TLR4 and c-Src. This study has confirmed the detrimental effect of EGFR activation in the pathogenesis of obesity-induced cardiac inflammatory injuries in experimental mice, and has demonstrated the TLR4/c-Src-mediated mechanisms for PA-induced EGFR activation. Our data suggest that EGFR may be a therapeutic target for obesity-related cardiovascular diseases.

OBJECTIVES:Apolipoprotein C3 (ApoC3) polymorphisms have been suggested to be associated with risk of coronary heart disease (CHD). However, the results of relevant studies were inconsistent. We aimed to systematically evaluate this issue. DESIGN:PubMed, EMBASE and Cochrane library databases (up to March 2013) were systematically searched to identify studies evaluating the association between ApoC3 polymorphisms and CHD risk. Two reviewers independently identified studies, extracted and analysed the data. Either a fixed-effects or a random-effects model was adopted to estimate overall ORs. STUDIES REVIEWED:Finally, 20 studies comprising 15 591 participants were included in this systematic review. Fifteen studies with 11 539 individuals were included in the meta-analysis of Sst I polymorphism, four studies comprising 3378 individuals assessed T-455C polymorphism, four studies with 3070 participants evaluated C-482T polymorphism and C1100T polymorphism was assessed by three studies comprising 4662 participants. RESULTS:Under dominant model, Sst I polymorphism was borderline significantly associated with CHD risk (S1S2+S2S2 vs S1S1, pooled OR=1.19, 95% CI 1.00 to 1.42). Subgroup analyses suggested that Sst I polymorphism was significantly associated with myocardial infarction (MI) risk (pooled OR=1.42, 95% CI 1.06 to 1.91), and Sst I polymorphism was statistically associated with CHD risk among Asian population (pooled OR=1.35, 95% CI 1.08 to 1.69) and in retrospective studies (pooled OR=1.30, 95% CI 1.04 to 1.61). A significant association was observed between T-455C polymorphism and CHD risk (TC+CC vs TT, pooled OR=1.22, 95% CI 1.06 to 1.42). A borderline significant association was suggested between T-455C polymorphism and MI risk (pooled OR=1.21, 95% CI 1.00 to 1.46). C-482T and C1100T polymorphisms were not indicated to be associated with CHD risk or MI risk. CONCLUSIONS:ApoC3 Sst I and T-455C polymorphisms might be associated with CHD risk.