Expression of genes associated with hemostasis disorders in patients with very high cardiovascular risk

Individuals at very high cardiovascular (CV) risk are a heterogeneous group, including patients with favorable and unfavorable outcomes, which prompt the search for new predictors associated with adverse CV disease outcomes. Especial attention is paid to studying the effect of expression of candidate genes encoding proteins that activate the hemostasis system in these pathological conditions.

Material and methods. Of the 100 study participants, 61 patients were selected for clinical and molecular analysis, including gene expression assessment, and were divided into 2 groups: the main group, patients with very high CV risk (n = 43), and the comparison group, individuals without a history of CV disease (n = 18). In those examined using the PCR method, an assessment was made of the relative expression level of SERPINE1, FGB, ITGA2 and ITGB3 genes associated with impaired hemostasis in patients with CV pathology.

Results. In patients with very high CV risk, the relative expression level of the SERPINE1 and ITGB3 genes is higher than in the comparison group. The ITGB3 gene mRNA content is significantly higher in patients with reduced left ventricular ejection fraction (LVEF) and multivessel coronary artery disease, the SERPINE1 gene mRNA – in patients 60 years of age and younger, with reduced LVEF, two-vessel coronary artery disease and right coronary artery stenting.

Conclusions. A significant increase in the relative expression level of ITGB3 and SERPINE1 genes was found compared to the background actin isoform used as a load control (ACTB) in patients with very high CV risk, including those with recurrent CV events. The expression level of these genes and the rate of its achievement in the group of patients with multifocal coronary artery disease and reduced LVEF, apparently, can be considered as a universal marker of the severity of CV diseases in patients with very high CV risk.

1. Averkov O.V., Arutyunyan G.K., Duplyakov D.V., Konstantinova E.V., Nikulina N.N., Shakhnovich R.M., Yavelov I.S., Yakovlev A.N., Abugov S.A., Alekyan B.G., … Yakushin S.S. 2024 Clinical practice guidelines for Acute myocardial infarction with ST segment elevation electrocardiogram. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2025;30(3):6306. doi: 10.15829/1560-4071-2025-6306

2. Kukharchuk V.V., Ezhov M.V., Sergienko I.V., Arabidze G.G., Bubnova M.G., Balakhonova T.V., Gurevich V.S., Kachkovsky M.A., Konovalov G.A., Konstantinov V.O., … Yakushin S.S. Diagnostics and correction of lipid metabolism disorders in order to prevent and treat of atherosclerosis. Russian recommendations VII revision. Aterosckleros i dyslipidemiya = Journal of Atherosclerosis and Dyslipidemias. 2020;1(1):7–40. doi: 10.34687/2219-8202.JAD.2020.01.0002

3. Piepoli M.F., Corrà U., Benzer C., Bjarnason-Wehrens B., Dendale P., Gaita D., McGee H., Mendes M., Niebauer J., Zwisler A.O., Schmid J.P.; Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation. Secondary prevention through cardiac rehabilitation: from knowledge to implementation. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation. Eur. J. Cardiovasc. Prev. Rehabil. 2010;17(1):1– 17. doi: 10.1097/HJR.0b013e3283313592

4. Plekhova N.G., Brodskaya T.A., Nevzorova V.A., Repina N.I., Eliseeva V.S. Single nucleotide substitution in the matrix metalloproteinase 9 gene hypertensive individuals of European and South Asian ethnicity in the Far Eastern Federal District. Kardiovaskulyarnaya terapiya I profilaktika = Cardiovascular Therapy and Prevention. 2022;21(1):2874 [In Russian]. doi: 10.15829/1728-8800-2022-2874.

5. Placencio V.R., DeClerck Y.A. Plasminogen activator inhibitor-1 in cancer: rational and insight for future therapeutic testing. Cancer Res. 2015;75(15):2969–2974. doi: 10.1158/0008-5472.CAN-15-0876

6. Divella R., Daniele A., Abbate I., Savino E., Casamassima P., Sciortino G., Simone G., GadaletaCaldarola G., Fazio V., Gadaleta C.D., Sabbà C., Mazzocca A. Circulating levels of PAI-1 and SERPINE1 4G/4G polymorphism are predictive of poor prognosis in HCC patients undergoing TACE. Transl. Oncol. 2015;8(4):273–278. doi: 10.1016/j.tranon.2015.05.002

7. Zhang X., Cai X., Pan J. Correlation between PAI-1 gene 4G/5G polymorphism and the risk of thrombosis in ph chromosome-negative myeloproliferative neoplasms. Clin. Appl. Thromb. Hemost. 2020;26:1076029620935207. doi: 10.1177/1076029620935207

8. Onalan O., Balta G., Oto A., Kabakci G., Tokgozoglu L, Aytemir K., Altay C., Aytemiz G., Nazli N. Plasminogen activator inhibitor-1 4G4G genotype is associated with myocardial infarction but not with stable coronary artery disease. J. Thromb. Thrombolysis. 2008;26(3):211–217. doi: 10.1007/s11239-007-0083-z

9. Sukhija R., Fahdi I., Garza L., Fink L., Scott M., Aude W., Pacheco R., Bursac Z., Grant A., Mehta J.L. Inflammatory markers, angiographic severity of coronary artery disease, and patient outcome. Am. J. Cardiol. 2007;99(7):879–884. doi: 10.1016/j.amjcard.2006.11.032

10. Rosenberg R.D., Arid W.C. Vascular-bed– specific hemostasis and hypercoagulable states. N. Engl. J. Med. 1999;340(20):1555–1564. doi: 10.1056/NEJM199905203402007

11. Hamsten A., Wiman B., Faire U., Blombäck M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N. Engl. J. Med. 1985;313(25):1557– 1563. doi: 10.1056/NEJM198512193132501

12. Sobel B.E., Woodcock-Mitchell J., Schneider D.J., Holt R.E., Marutsuka K., Gold H. Increased plasminogen activator inhibitor type 1 in coronary artery atherectomy specimens from type 2 diabetic compared with nondiabetic patients. Circulation. 1998;97(22):2213–2221. doi: 10.1161/01.cir.97.22.2213

13. Sharma R.K., Voelker D.J., Sharma R., Reddy H.K., Dod H., Marsh J.D. Evolving role of platelet function testing in coronary artery interventions. Vasc. Health. Risk Manag. 2012;8:65–75. doi: 10.2147/VHRM.S28090

14. Sheikhvatan M., Boroumand M.A., Behmanesh M., Ziaee S., Cheraghee S. Integrin Beta 3 gene polymorphism and risk for myocardial infarction in premature coronary disease. Iran. J. Biotechnol. 2019;17(2):79–88. doi: 10.21859/ijb.1921.