{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T20:28:37Z","timestamp":1785875317246,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Minister of Science and Higher Education","award":["002\/RID\/2018-19"],"award-info":[{"award-number":["002\/RID\/2018-19"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Coronary artery disease (CAD) is a syndrome resulting from myocardial ischaemia of heterogeneous pathomechanism. Environmental and genetic factors contribute to its development. Atherosclerotic plaques that significantly narrow the lumen of coronary arteries cause symptoms of myocardial ischaemia. Acute coronary incidents are most often associated with plaque rupture or erosion accompanied by local activation of the coagulation system with thrombus formation. Plaque formation and stability are influenced by endothelial function and vascular smooth muscle cell function. In this study, we investigated the association between polymorphisms in genes affecting endothelial and vascular smooth muscle cell (VSMC) function and the occurrence of unstable angina pectoris. The aim of this study was to evaluate the association between the PECAM1 (rs1867624), COL4A2 (rs4773144), PHACTR1 (rs9349379) and LMOD1 (rs2820315) gene polymorphisms and the risk of unstable angina. The study included 232 patients with unstable angina diagnosed on the basis of clinical symptoms and coronary angiography and 144 healthy subjects with no significant coronary lumen stenosis at coronary angiography. There were no statistically significant differences in the distribution of COL4A2 rs4773144 and PECAM1 rs1867624 gene polymorphisms between patients with unstable angina and control subjects. In patients with unstable angina, there was an increased frequency of PHACTR1 rs9349379 G allele carriers (GG and AG genotypes) (GG+AG vs. AA, OR 1.71; 95% CI 1.10\u20132.66, p = 0.017) and carriers of the LMOD1 rs2820315 T allele (TT and CT genotypes) (TT+CT vs. CC, OR 1.65; 95% CI 1.09\u20132.51, p = 0.019) compared to the control group. The association between these alleles and unstable angina was confirmed by multivariate logistic regression analysis, in which the number of G (PHACTR1 rs9349379) and T (LMOD1 rs2820315) alleles was an independent risk factor for unstable angina. The results suggest an association between PHACTR1 rs9349379 and LMOD1 rs2820315 polymorphisms and the risk of unstable angina.<\/jats:p>","DOI":"10.3390\/jcm11020373","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T10:57:37Z","timestamp":1642071457000},"page":"373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["PECAM1, COL4A2, PHACTR1, and LMOD1 Gene Polymorphisms in Patients with Unstable Angina"],"prefix":"10.3390","volume":"11","author":[{"given":"Krzysztof","family":"Kosi\u0144ski","sequence":"first","affiliation":[{"name":"Department of Cardiology, Hospital in Szczecin, Arkonska 4, 71-455 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8393-9627","authenticated-orcid":false,"given":"Damian","family":"Malinowski","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9415-2758","authenticated-orcid":false,"given":"Krzysztof","family":"Safranow","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4809-415X","authenticated-orcid":false,"given":"Violetta","family":"Dziedziejko","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6557-1208","authenticated-orcid":false,"given":"Andrzej","family":"Pawlik","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1161\/CIRCRESAHA.115.306566","article-title":"Genetics of Coronary Artery Disease","volume":"118","author":"McPherson","year":"2016","journal-title":"Circ. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"168516","DOI":"10.1056\/NEJMra043430","article-title":"Inflammation, atherosclerosis, and coronary artery disease","volume":"352","author":"Hansson","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.2174\/138161209787846757","article-title":"The Extracellular Matrix of Blood Vessels","volume":"15","author":"Eble","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1161\/CIRCRESAHA.115.306301","article-title":"Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis","volume":"118","author":"Gimbrone","year":"2016","journal-title":"Circ. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/ncpcardio1397","article-title":"Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology","volume":"6","author":"Davies","year":"2009","journal-title":"Nat. Clin. Pract. Cardiovasc. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1161\/CIRCULATIONAHA.105.567297","article-title":"Tissue factor in cardiovascular diseases: Molecular mechanisms and clinical implications","volume":"113","author":"Steffel","year":"2006","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e002327","DOI":"10.1161\/CIRCGEN.118.002327","article-title":"Confirmation of Causal rs9349379- PHACTR1 Expression Quantitative Trait Locus in Human-Induced Pluripotent Stem Cell Endothelial Cells","volume":"11","author":"Wang","year":"2018","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1161\/ATVBAHA.115.305534","article-title":"Myocardial Infarction-Associated SNP at 6p24 Interferes With MEF2 Binding and Associates with PHACTR1 Expression Levels in Human Coronary Arteries","volume":"35","author":"Beaudoin","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4131","DOI":"10.1242\/dev.008367","article-title":"MEF2: A central regulator of diverse developmental programs","volume":"134","author":"Potthoff","year":"2007","journal-title":"Development"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/j.biochi.2011.07.010","article-title":"Depletion of the novel protein PHACTR-1 from human endothelial cells abolishes tube formation and induces cell death receptor apoptosis","volume":"93","author":"Jarray","year":"2011","journal-title":"Biochimie"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.yjmcc.2006.05.023","article-title":"Regulation of endothelial and myocardial NO synthesis by multi-site eNOS phosphorylation","volume":"42","author":"Mount","year":"2007","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1161\/CIRCULATIONAHA.110.974899","article-title":"Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction","volume":"124","author":"Kavousi","year":"2011","journal-title":"Circulation"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Myocardial Infarction Genetics Consortium, Kathiresan, S., Voight, B.F., Purcell, S., Musunuru, K., Ardissino, D., Mannucci, P.M., Anand, S., Engert, J.C., and Samani, N.J. (2009). Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat. Genet., 41, 334\u2013341.","DOI":"10.1038\/ng.327"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hager, J., Kamatani, Y., Cazier, J.B., Youhanna, S., Ghassibe-Sabbagh, M., Platt, D.E., Abchee, A.B., Romanos, J., Khazen, G., and Othman, R. (2012). Genome-wide association study in a Lebanese cohort confirms PHACTR1 as a major determinant of coronary artery stenosis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038663"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Hern\u00e1ndez, N., Vargas-Alarc\u00f3n, G., Posadas-S\u00e1nchez, R., Mart\u00ednez-Rodr\u00edguez, N., Tovilla-Z\u00e1rate, C.A., Rodr\u00edguez-Cort\u00e9s, A.A., P\u00e9rez-M\u00e9ndez, O., Blachman-Braun, R., and Rodr\u00edguez-P\u00e9rez, J.M. (2016). PHACTR1 Gene Polymorphism Is Associated with Increased Risk of Developing Premature Coronary Artery Disease in Mexican Population. Int. J. Environ. Res. Public Health, 13.","DOI":"10.3390\/ijerph13080803"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1136\/postgradmedj-2018-136298","article-title":"PHACTR1 gene polymorphism with the risk of coronary artery disease in Chinese Han population","volume":"95","author":"Chen","year":"2019","journal-title":"Postgrad. Med. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.cell.2017.06.049","article-title":"A Genetic Variant Associated with Five Vascular Diseases Is a Distal Regulator of Endothelin-1 Gene Expression","volume":"170","author":"Gupta","year":"2017","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.1093\/eurheartj\/ehz915","article-title":"Genetic dysregulation of endothelin-1 is implicated in coronary microvascular dysfunction","volume":"41","author":"Ford","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e145275","DOI":"10.1172\/JCI145275","article-title":"Deficiency of macrophage PHACTR1 impairs efferocytosis and promotes atherosclerotic plaque necrosis","volume":"131","author":"Kasikara","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3389\/fcvm.2017.00002","article-title":"Eating the Dead to Keep Atherosclerosis at Bay","volume":"4","author":"Brophy","year":"2017","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1161\/CIRCRESAHA.109.208389","article-title":"Vascular smooth muscle cell apoptosis induces interleukin-1-directed inflammation: Effects of hyperlipidemia-mediated inhibition of phagocytosis","volume":"106","author":"Clarke","year":"2010","journal-title":"Circ. Res."},{"key":"ref_22","first-page":"239","article-title":"Leiomodin 3 and tropomodulin 4 have overlapping functions during skeletal myofibrillogenesis","volume":"128","author":"Nworu","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tolkatchev, D., Gregorio, C.C., and Kostyukova, A.S. (FEBS J., 2021). The role of leiomodin in actin dynamics: A new road or a secret gate, FEBS J., in press.","DOI":"10.1111\/febs.16128"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/ng.3874","article-title":"Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms","volume":"49","author":"Howson","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Nanda, V., Wang, T., Pjanic, M., Liu, B., Nguyen, T., Matic, L.P., Hedin, U., Koplev, S., Ma, L., and Franz\u00e9n, O. (2018). Functional regulatory mechanism of smooth muscle cell-restricted LMOD1 coronary artery disease locus. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007755"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1161\/ATVBAHA.116.307893","article-title":"Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated With Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM","volume":"36","author":"Rykaczewska","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Levula, M., Oksala, N., Airla, N., Zeitlin, R., Salenius, J.P., J\u00e4rvinen, O., Venermo, M., Partio, T., Saarinen, J., and Somppi, T. (2012). Genes involved in systemic and arterial bed dependent atherosclerosis--Tampere Vascular study. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033787"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12092","DOI":"10.1038\/ncomms12092","article-title":"Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci","volume":"7","author":"Miller","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1161\/ATVBAHA.119.312141","article-title":"Genetic Insights into Smooth Muscle Cell Contributions to Coronary Artery Disease","volume":"39","author":"Wong","year":"2019","journal-title":"Arterioscler. Thromb. Vasc Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1161\/CIRCRESAHA.120.315935","article-title":"CD31 as a Therapeutic Target in Atherosclerosis","volume":"126","author":"Caligiuri","year":"2020","journal-title":"Circ. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1242\/jcs.082271","article-title":"Relative contribution of PECAM-1 adhesion and signaling to the maintenance of vascular integrity","volume":"124","author":"Privratsky","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1002\/cbf.3155","article-title":"Platelet endothelial cell adhesion molecule-1 (PECAM1) plays a critical role in the maintenance of human vascular endothelial barrier function","volume":"33","author":"Ren","year":"2015","journal-title":"Cell Biochem. Funct."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1161\/ATVBAHA.108.172270","article-title":"Site-specific effects of PECAM-1 on atherosclerosis in LDL receptor-deficient mice","volume":"28","author":"Goel","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1093\/cvr\/cvz132","article-title":"Mechanotransduction, immunoregulation, and metabolic functions of CD31 in cardiovascular pathophysiology","volume":"115","author":"Caligiuri","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.atherosclerosis.2015.08.008","article-title":"Functional interaction between COL4A1\/COL4A2 and SMAD3 risk loci for coronary artery disease","volume":"242","author":"Turner","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yang, W., Ng, F.L., Chan, K., Pu, X., Poston, R.N., Ren, M., An, W., Zhang, R., Wu, J., and Yan, S. (2016). Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1\/COL4A2 Locus Affects COL4A1\/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006127"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/ng.784","article-title":"Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease","volume":"43","author":"Schunkert","year":"2011","journal-title":"Nat. Genet."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/2\/373\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:28:54Z","timestamp":1760365734000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/2\/373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,13]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["jcm11020373"],"URL":"https:\/\/doi.org\/10.3390\/jcm11020373","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,13]]}}}