{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:46:45Z","timestamp":1787586405485,"version":"build-2736575974"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This aim of this study is to screen the differential molecules of kidney deficiency and blood stasis (KDBS) syndrome in coronary heart disease by high-throughput sequencing. In addition, the study aims to verify the alterations in the expression levels of miR-4685-3p and its regulated downstream, namely, C1QC, C4, and C5, using quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA), and to determine whether the complement and coagulation cascade pathway is the specific pathogenic pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients diagnosed with unstable angina pectoris with KDBS syndrome, patients with non-kidney deficiency blood stasis (NKDBS) syndrome, and a Normal group were recruited. The clinical symptoms of each group were further analyzed. Illumina's NextSeq 2000 sequencing platform and FastQC software were used for RNA sequencing and quality control. DESeq software was used for differential gene expression (DGE) analysis. qPCR and ELISA verification were performed on DGE analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The DGE profiles of 77 miRNA and 331 mRNA were selected. The GO enrichment analysis comprised 43 biological processes, 49 cell components, and 42 molecular functions. The KEGG enrichment results included 40 KEGG pathways. The PCR results showed that, compared with the Normal group, the miR-4685-3p levels decreased in the CHD_KDBS group (<jats:italic>P<\/jats:italic>\u2009=\u20090.001), and were found to be lower than those observed in the CHD_NKDBS group. The downstream mRNA C1 regulated by miR-4685-3p showed an increasing trend in the CHD_KDBS group, which was higher than that in the Normal group (<jats:italic>P<\/jats:italic>\u2009=\u20090.0019). The mRNA C4 and C5 in the CHD_KDBS group showed an upward trend, but the difference was not statistically significant. ELISA was utilized for the detection of proteins associated with the complement and coagulation cascade pathway. It was found that the expression level of C1 was significantly upregulated in the CHD_KDBS group compared with the Normal group (<jats:italic>P<\/jats:italic>\u2009&amp;lt;\u20090.0001), which was seen to be higher than that in the CHD_NKDBS group (<jats:italic>P<\/jats:italic>\u2009&amp;lt;\u20090.0001). The expression levels of C4 and C5 in the CHD_KDBS group were significantly lower than the Normal group, and were lower than that in the CHD_NKDBS group (<jats:italic>P<\/jats:italic>\u2009&amp;lt;\u20090.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The occurrence of CHD_KDBS might be related to the activation of the complement and coagulation cascade pathway, which is demonstrated by the observed decrease in miR-4685-3p and the subsequent upregulation of its downstream C1QC. In addition, the expression levels of complement C4 and C5 were found to be decreased, which provided a research basis for the prevention and treatment of this disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2023.1186297","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T08:49:54Z","timestamp":1698655794000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification and analysis of differential miRNA\u2013mRNA interactions in coronary heart disease: an experimental screening approach"],"prefix":"10.3389","volume":"10","author":[{"given":"Jie","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanchun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuo","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyuan","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoqiang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshan","family":"Hui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peirong","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,30]]},"reference":[{"key":"B1","year":""},{"key":"B2","doi-asserted-by":"publisher","first-page":"553","DOI":"10.3969\/j.issn.1000-3614.2022.06.001","article-title":"Overview of China cardiovascular health and disease report 2021","volume":"37","year":"2022","journal-title":"Chin J Circ"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.3969\/j.issn.1005-2194.2006.15.005","article-title":"Interventional treatment of unstable angina and non-ST-elevation myocardial infarction","volume":"26","author":"Han","year":"2006","journal-title":"Chin J Pract Intern Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1636145","DOI":"10.1155\/2022\/1636145","article-title":"Metabolomics deciphering the potential biomarkers of Hengqing I prescription against vascular dementia","volume":"2022","author":"Meng","year":"2022","journal-title":"Evid Based Complement Alternat Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"920","DOI":"10.13288\/j.11-2166\/r.2007.10.029","article-title":"Study on syndrome elements and indications in coronary heart disease","volume":"48","author":"Wang","year":"2007","journal-title":"Tradit Chin Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"211","DOI":"10.3969\/j.issn.1006-3250.2008.03.024","article-title":"Study on the extraction and combination of angina syndrome in 1069 cases of coronary heart disease by entropy accumulation pile method in complex systems","volume":"14","author":"Wang","year":"2008","journal-title":"Chin J Basic Med Tradit Chin Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1161\/CIRCULATIONAHA.113.001904","article-title":"Inhibition of microRNA-92a protects against ischemia\/reperfusion injury in a large-animal model","volume":"128","author":"Hinkel","year":"2013","journal-title":"Circulation"},{"key":"B8","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/nm.3487","article-title":"MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1","volume":"20","author":"Schober","year":"2014","journal-title":"Nat Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1161\/CIRCRESAHA.109.215566","article-title":"Circulating microRNAs in patients with coronary artery disease","volume":"107","author":"Fichtlscherer","year":"2010","journal-title":"Circ Res"},{"key":"B10","volume-title":"Molecular mechanism of microRNAs in blood stasis of coronary heart disease","author":"Bao","year":"2013"},{"key":"B11","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nature21025","article-title":"An Argonaute phosphorylation cycle promotes microRNA-mediated silencing","volume":"542","author":"Golden","year":"2017","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1126\/science.aaa1738","article-title":"Gene expression. microRNA control of protein expression noise","volume":"348","author":"Schmiedel","year":"2015","journal-title":"Science"},{"key":"B13","first-page":"94","article-title":"Effect of Xiangdan injection on gene expression of endothelial-derived vasoactive factor in blood stasis of coronary heart disease","volume":"2","author":"Wu","year":"2004","journal-title":"J Integr Med"},{"key":"B14","first-page":"1313","article-title":"Differential gene screening and functional path analysis related to blood stasis in coronary heart disease","volume":"32","author":"Yuan","year":"2012","journal-title":"Chin J Integr Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2022","DOI":"10.1161\/CIR.0b013e31820f2f3e","article-title":"2011 ACCF\/AHA focused update of the guidelines for the management of patients with unstable angina\/non-ST-elevation myocardial infarction (updating the 2007 guideline): a report of the American College of Cardiology Foundation\/American Heart Association task force on practice guidelines","volume":"123","author":"Wright","year":"2011","journal-title":"Circulation"},{"key":"B16","doi-asserted-by":"publisher","first-page":"539","DOI":"10.13288\/j.11-2166\/r.2018.06.023","article-title":"Diagnostic criteria for angina syndrome in coronary heart disease","volume":"59","author":"Wang","year":"2018","journal-title":"J Tradit Chin Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"154","DOI":"10.7661\/j.cjim.20171214.330","article-title":"Differential diagnostic criteria for the main symptom types of angina pectoris in coronary heart disease","volume":"38","year":"2018","journal-title":"Chin J Integr Tradit West Med"},{"key":"B18","first-page":"598","article-title":"Reference standard for false evidence differentiation in Traditional Chinese Medicine","volume":"10","author":"Shen","year":"1986","journal-title":"Chin J Integr Med"},{"key":"B19","volume-title":"Screening and verification of miRNA-mRNA in renal deficiency and blood stasis in unstable angina pectoris of coronary heart disease","author":"Liu","year":"2022"},{"key":"B20","doi-asserted-by":"publisher","first-page":"109655","DOI":"10.1016\/j.biopha.2019.109655","article-title":"Uncovering the protective mechanism of Huoxue Anxin recipe against coronary heart disease by network analysis and experimental validation","volume":"121","author":"Wang","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"B21","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1097\/TA.0000000000000129","article-title":"Complement mediates a primed inflammatory response after traumatic lung injury","volume":"76","author":"Hoth","year":"2014","journal-title":"J Trauma Acute Care Surg"},{"key":"B22","doi-asserted-by":"publisher","first-page":"R269","DOI":"10.1186\/ar4117","article-title":"Autoantibody-mediated arthritis in the absence of C3 and activating Fc\u03b3 receptors: C5 is activated by the coagulation cascade","volume":"14","author":"Auger","year":"2012","journal-title":"Arthritis Res Ther"},{"key":"B23","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1161\/ATVBAHA.113.302378","article-title":"Erythrocyte-derived microvesicles amplify systemic inflammation by thrombin-dependent activation of complement","volume":"34","author":"Zecher","year":"2014","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1038\/nrd4657","article-title":"Complement, a target for therapy in inflammatory and degenerative diseases","volume":"14","author":"Morgan","year":"2015","journal-title":"Nat Rev Drug Discov"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3831","DOI":"10.4049\/jimmunol.1203487","article-title":"Complement in immune and inflammatory disorders: pathophysiological mechanisms","volume":"190","author":"Ricklin","year":"2013","journal-title":"J Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1038\/ni.1923","article-title":"Complement: a key system for immune surveillance and homeostasis","volume":"11","author":"Ricklin","year":"2010","journal-title":"Nat Immunol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"580","DOI":"10.3760\/cma.j.issn.1009-9158.2015.09.002","article-title":"Research status and prospect of complement system and kidney disease","volume":"9","author":"Li","year":"2015","journal-title":"Chin J Lab Med"},{"key":"B28","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/nm1419","article-title":"Generation of C5a in the absence of C3: a new complement activation pathway","volume":"12","author":"Huber-Lang","year":"2006","journal-title":"Nat Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1067\/msy.1998.91489","article-title":"Complement inhibition prevents gut ischemia and endothelial cell dysfunction after hemorrhage\/resuscitation","volume":"124","author":"Fruchterman","year":"1998","journal-title":"Surgery"},{"key":"B30","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1055\/s-0038-1655974","article-title":"C5a induces tissue factor activity on endothelial cells","volume":"77","author":"Ikeda","year":"1997","journal-title":"Thromb Haemost"},{"key":"B31","doi-asserted-by":"publisher","first-page":"4794","DOI":"10.4049\/jimmunol.177.7.4794","article-title":"A novel C5a receptor-tissue factor cross-talk in neutrophils links innate immunity to coagulation pathways","volume":"177","author":"Ritis","year":"2006","journal-title":"J Immunol"},{"key":"B32","volume-title":"Pathway-related modules to study the myoprotective effects of sevoflurane and propofol in OPCABG center","author":"Bu","year":"2019"},{"key":"B33","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s00395-015-0485-6","article-title":"Complement system modulation as a target for treatment of arrhythmogenic cardiomyopathy","volume":"110","author":"Mavroidis","year":"2015","journal-title":"Basic Res Cardiol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1161\/hc3801.096353","article-title":"Complement activation in patients with congestive heart failure: effect of high-dose intravenous immunoglobulin treatment","volume":"104","author":"Aukrust","year":"2001","journal-title":"Circulation"},{"key":"B35","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1097\/FJC.0b013e31822a7a09","article-title":"Inhibition of inflammation and fibrosis by a complement C5a receptor antagonist in DOCA-salt hypertensive rats","volume":"58","author":"Iyer","year":"2011","journal-title":"J Cardiovasc Pharmacol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/s0002-9440(10)64201-0","article-title":"Complement and dilated cardiomyopathy: a role of sublytic terminal complement complex-induced tumor necrosis factor-alpha synthesis in cardiac myocytes","volume":"161","author":"Zwaka","year":"2002","journal-title":"Am J Pathol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1111\/j.1365-2362.2004.01425.x","article-title":"C-reactive protein and complement depositions in human infarcted myocardium are more extensive in patients with reinfarction or upon treatment with reperfusion","volume":"34","author":"Nijmeijer","year":"2004","journal-title":"Eur J Clin Invest"},{"key":"B38","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/s41380-021-01197-9","article-title":"Dysregulation of complement and coagulation pathways: emerging mechanisms in the development of psychosis","volume":"27","author":"Heurich","year":"2022","journal-title":"Mol Psychiatry"},{"key":"B39","doi-asserted-by":"publisher","first-page":"32","DOI":"10.3969\/j.issn.1009-6213.2013.01.012","article-title":"Congenital immunity and blood coagulation","volume":"19","author":"Wu","year":"2013","journal-title":"Thromb Haemost"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1038\/s41591-020-1021-2","article-title":"Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection","volume":"26","author":"Ramlall","year":"2020","journal-title":"Nat Med"},{"key":"B41","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3969\/j.issn.1009-0002.2019.01.011","article-title":"Analysis of plasma exosome proteome in lung cancer patients","volume":"30","author":"Zhong","year":"2019","journal-title":"Biotechnol Commun"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2957","DOI":"10.19381\/j.issn.1001-7585.2020.18.001","article-title":"Hepatocellular carcinoma-derived blood-associated exosome components participate in the innate immunity of tumor tissues through complement and coagulation cascade","volume":"33","author":"Ling","year":"2020","journal-title":"Med Princ Pract"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2023.1186297\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T08:50:18Z","timestamp":1698655818000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2023.1186297\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,30]]},"references-count":42,"alternative-id":["10.3389\/fcvm.2023.1186297"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2023.1186297","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,30]]},"article-number":"1186297"}}