Preview

Complex Issues of Cardiovascular Diseases

Advanced search

A modern view on the diagnostic role of endothelial dysfunction biomarkers and the possibilities of its correction

https://doi.org/10.17802/2306-1278-2022-11-4S-194-207

Abstract

Highlights. The article presents a review of literature data on the diagnostic role of endothelial dysfunction biomarkers. The review provides an overview of the main indicators, their significance in various pathologies, and presents possible therapeutic strategies for preventing endothelial dysfunction.

Abstract. Endothelial dysfunction is a characteristic feature of each stage of the cardiovascular continuum – a series of events from hypertension to the development of atherosclerosis and coronary heart disease, thrombus formation, myocardial infarction, and heart failure. Due to the prominent role of endothelial dysfunction in the pathogenesis of many vascular diseases, it is a significant therapeutic target. It is important to note that circulating markers of endothelial activation and damage characterize the severity of the disease and can be used to evaluate the efficacy of treatment and subsequent prognosis. The purpose of this review is to provide up–to-date data on endothelial function, discussing its clinical relevance in the cardiovascular continuum, the latest insights in molecular and cellular biology, and their implications for clinical practice, with a focus on new methods of therapeutic approaches for correcting endothelial dysfunction.

About the Authors

E. A. Zakharyan
Medical Academy named after S.I. Georgievsky of the V.I. Vernadsky Crimean Federal University
Russian Federation

Elena A. Zakharyan - PhD, Associate Professor at the Department of Internal Medicine No. 1, Medical Academy named after S.I. Georgievsky of the V.I. Vernadsky Crimean Federal University.

5/7, Lenina Blvd., Simferopol, Crimea, 295051


Competing Interests:

No



E. S. Ageeva
Medical Academy named after S.I. Georgievsky of the V.I. Vernadsky Crimean Federal University
Russian Federation

Elizaveta S. Ageeva - PhD, Associate Professor, Head of the Department of Biology, Medical Academy named after S.I. Georgievsky of the V.I. Vernadsky Crimean Federal University.

5/7, Lenina Blvd., Simferopol, Crimea, 295051


Competing Interests:

No



Yu. I. Shramko
Medical Academy named after S.I. Georgievsky of the V.I. Vernadsky Crimean Federal University
Russian Federation

Yuliana I. Shramko - PhD, Associate Professor at the Department of General and Clinical Pathophysiology, Medical Academy named after S.I. Georgievsky of the V.I. Vernadsky Crimean Federal University.

5/7, Lenina Blvd., Simferopol, Crimea, 295051


Competing Interests:

No



K. D. Malyi
Medical Academy named after S.I. Georgievsky of the V.I. Vernadsky Crimean Federal University
Russian Federation

Konstantin D. Malyi - PhD, Associate Professor at the Department of Biochemistry, Medical Academy named after S.I. Georgievsky of the V.I. Vernadsky Crimean Federal University.

5/7, Lenina Blvd., Simferopol, Crimea, 295051


Competing Interests:

No



A. K. Gurtovaya
Medical Academy named after S.I. Georgievsky of the V.I. Vernadsky Crimean Federal University
Russian Federation

Anna K. Gurtovaya - Laboratory Assistant at the  Center for the Collective Use of Scientific Equipment “Molecular Biology”, Medical Academy named after S.I. Georgievsky of the V.I. Vernadsky Crimean Federal University.

5/7, Lenina Blvd., Simferopol, Crimea, 295051


Competing Interests:

No



R. E. Ibragimova
Medical Academy named after S.I. Georgievsky of the V.I. Vernadsky Crimean Federal University
Russian Federation

Regina E. Ibragimova - Student at the Department of Internal Medicine No. 1, Medical Academy named after S.I. Georgievsky of the V.I. Vernadsky Crimean Federal University.

5/7, Lenina Blvd., Simferopol, Crimea, 295051


Competing Interests:

No



References

1. Alexander Y., Osto E., Schmidt-Trucksäss A., Shechter M., Trifunovic D., Duncker D.J., Aboyans V., Bäck M., Badimon L., Cosentino F., De Carlo M., Dorobantu M., Harrison D.G., Guzik T.J., Hoefer I., Morris P.D., Norata G.D., Suades R., Taddei S., Vilahur G., Waltenberger J., Weber C., Wilkinson F., Bochaton-Piallat M.L., Evans P.C. Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis. Cardiovasc Res. 2021;117(1):29-42. doi: 10.1093/cvr/cvaa085.

2. Leite A.R., Borges-Canha M., Cardoso R., Neves J.S., Castro-Ferreira R., Leite-Moreira A. Novel Biomarkers for Evaluation of Endothelial Dysfunction. Angiology. 2020; 71(5): 397-410. doi:10.1177/0003319720903586.

3. Medina-Leyte D.J., Zepeda-García O., Domínguez-Pérez M., González-Garrido A., Villarreal-Molina T., Jacobo-Albavera L. Endothelial Dysfunction, Inflammation and Coronary Artery Disease: Potential Biomarkers and Promising Therapeutical Approaches. International journal of molecular sciences. 2021; 22(8): 3850. doi:10.3390/ijms22083850.

4. Xu S., Ilyas I., Little P.J., Li H., Kamato D., Zheng X., Luo S., Li Z., Liu P., Han J., Harding I.C., Ebong E.E., Cameron S.J., Stewart A.G., Weng J. Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies. Pharmacol Reviews. 2021; 73(3): 924-967. doi:10.1124/pharmrev.120.000096.

5. Incalza M.A., D'Oria R., Natalicchio A., Perrini S., Laviola L., Giorgino F.. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascular pharmacology. 2018; 100: 1-19. doi:10.1016/j.vph.2017.05.005.

6. Balta S. Endothelial Dysfunction and Inflammatory Markers of Vascular Disease. Current Vascular Pharmacology. 2021;19(3):243-249. doi:10.2174/1570161118666200421142542.

7. Liang S., Zhang J., Ning R., Du Z., Liu J., Batibawa J.W., Duan J., Sun Z.. The critical role of endothelial function in fine particulate matter-induced atherosclerosis. Particle and Fibre Toxicology. 2020; 17(1): 61. doi:10.1186/s12989-020-00391-x.

8. Lugo-Gavidia L.M., Burger D., Matthews V.B., Nolde J.M., Galindo Kiuchi M., Carnagarin R., Kannenkeril D., Chan J., Joyson A., Herat L.Y., Azzam O., Schlaich M.P. Role of Microparticles in Cardiovascular Disease: Implications for Endothelial Dysfunction, Thrombosis, and Inflammation. Hypertension. 2021; 77(6): 1825-1844. doi:10.1161/HYPERTENSIONAHA.121.16975.

9. Samolyuk M.O., Grigoryeva N.Yu. Evaluation of endothelial dysfunction and possibilities of its correction at the present stage in patients with cardiovascular diseases. Cardiology. 2019; 59 (3): 4-9. doi:10.18087/cardio.2524. (In Russian)

10. Nikitin Y.P., Nikolaev K.Y., Ragino Y.I., Malyutina S.K., Zhuravskaya E.Ya., Polonskaya Ya.V. et al. Endothelial dysfunction, hypertension, and atherosclerosis. Novosibirsk; 2014 (In Russian)

11. Strukova E. V., Ragino Y. I., Maksimov V. N. Biochemical markers of endothelial dysfunction and hemostasis in atherosclerosis and the genes responsible for their regulation. Atherosclerosis. 2017; 13 (1): 49-56.(In Russian)

12. Dowsett L., Higgins E., Alanazi S., Alshuwayer N.A., Leiper F.C., Leiper J. ADMA: A Key Player in the Relationship between Vascular Dysfunction and Inflammation in Atherosclerosis. Journal of Clinical Medicine. 2020; 9 (9): 3026. doi:10.3390/jcm9093026.

13. Jud P., Hafner F., Verheyen N., Meinitzer A., Gary T., Brodmann M., Seinost G., Hackl G. Homoarginine/ADMA ratio and homoarginine/SDMA ratio as independent predictors of cardiovascular mortality and cardiovascular events in lower extremity arterial disease. Scientific Reports. 2018; 8: 14197.

14. Liu Y., Paauwe M., Nixon A.B., Hawinkels L.J.A.C. Endoglin Targeting: Lessons Learned and Questions That Remain. International Journal of Molecular Sciences. 2020; 22(1):147. doi:10.3390/ijms22010147.

15. Shyu K.G. The Role of Endoglin in Myocardial Fibrosis. Acta Cardiologica Sinica. 2017;33(5):461-467. doi:10.6515/acs20170221b.

16. Rossi E., Bernabeu C., Smadja D.M. Endoglin as an Adhesion Molecule in Mature and Progenitor Endothelial Cells: A Function Beyond TGF-β. Front Med (Lausanne). 2019;6:10. doi: 10.3389/fmed.2019.00010.

17. Vicen M., Igreja Sá I.C., Tripská K., Vitverová B., Najmanová I., Eissazadeh S., Micuda S., Nachtigal P.. Membrane and soluble endoglin role in cardiovascular and metabolic disorders related to metabolic syndrome. Cellular and Molecular Life Sciences. 2021;78(6):2405-2418. doi:10.1007/s00018-020-03701-w.

18. Margioula-Siarkou G., Margioula-Siarkou C., Petousis S., Margaritis K., Vavoulidis E., Gullo G., Alexandratou M., Dinas K., Sotiriadis A., Mavromatidis G. The role of endoglin and its soluble form in pathogenesis of preeclampsia. Molecular and Cellular Biochemistry. 2022; 477(2): 479-491. doi:10.1007/s11010-021-04294-z.

19. Zhang J. Biomarkers of endothelial activation and dysfunction in cardiovascular diseases. Reviews in Cardiovascular Medicine. 2022; 23(2): 73. doi:10.31083/j.rcm2302073.

20. Balta S., Balta I., Mikhailidis D.P. Endocan: a new marker of endothelial function. Current Opinion in Cardiology. 2021; 36(4): 462-468. doi:10.1097/HCO.0000000000000867.

21. Hsiao S.Y., Kung C.T., Tsai N.W., Su C.M., Huang C.C., Lai Y.R., Wang H.C., Cheng B.C., Su Y.J., Lin W.C., Chiang Y.F., Lu C.H. Concentration and value of endocan on outcome in adult patients after severe sepsis. Clin Chim Acta. 2018;483:275-280. doi: 10.1016/j.cca.2018.05.007.

22. Kundi H., Balun A., Cicekcioglu H., Karayigit O., Topcuoglu C., Kilinckaya M.F., Kiziltunc E., Cetin M., Ornek E. Admission endocan level may be a useful predictor for in-hospital mortality and coronary severity index in patients with ST-segment elevation myocardial infarction. Angiology. 2017; 68: 46-51. doi:10.1177/0003319716646932.

23. Stepanova T.V., Ivanov A.N., Tereshkina N.E., Popyhova E.B., Lagutina D.D. Markers of endothelial dysfunction: pathogenetic role and diagnostic significance (literature review). Clinical Laboratory Diagnostics.2019; 64(1): 34-41. doi:10.18821/0869-2084-2019-64-1-34-41. (In Russian)

24. Zhou Y., Zhu X., Cui H., Shi J., Yuan G., Shi S., Hu Y. The Role of the VEGF Family in Coronary Heart Disease. Frontiers in cardiovascular medicine. 2021; 8: 738325. doi:10.3389/fcvm.2021.738325.

25. Dabravolski S.A., Khotina V.A., Omelchenko A.V., Kalmykov V.A., Orekhov A.N. The Role of the VEGF Family in Atherosclerosis Development and Its Potential as Treatment Targets. International Journal of Molecular Sciences. 2022; 23(2): 931. doi:10.3390/ijms23020931.

26. Garcia R., Bouleti C., Sirol M., Logeart D., Monnot C., Ardidie-Robouant C., Caligiuri G., Mercadier J.J., Germain S. VEGF-A plasma levels are associated with microvascular obstruction in patients with ST-segment elevation myocardial infarction. International Journal of Cardiology. 2019; 291: 19-24. doi:10.1016/j.ijcard.2019.02.067.

27. Popkov V.M., Ponukalin A.N., Zakharova N.B. Vascular endothelial growth factor in diagnostics of metastases of a muscleinvasive bladder cancer. Onkourologiya. 2016; 12(2): 53– 57. doi: 10.17650/1726-9776-2016-12-2-53-57 ( In Russian)

28. Park J.Y., Lee J.Y., Lee Y.Y., Shim S.H., Suh D.H., Kim J.W. Major clinical research advances in gynecologic cancer in 2021. Journal of Gynecologic Oncology. 2022; 33(2): 43. doi:10.3802/jgo.2022.33.e43.

29. Flower V.A., Barratt S.L., Ward S., Pauling J.D. The Role of Vascular Endothelial Growth Factor in Systemic Sclerosis. Current rheumatology reviews. 2019; 15(2): 99-109. doi:10.2174/1573397114666180809121005.

30. Moreira F. R. C., de Oliveira T.A., Ramos N.E., Abreu M.A.D., Simões E Silva A.C. The role of renin angiotensin system in the pathophysiology of rheumatoid arthritis. Molecular Biology Reports. 2021; 48(9): 6619-6629. doi:10.1007/s11033-021-06672-8.

31. Troncoso M. F., Ortiz-Quintero J., Garrido-Moreno V., Sanhueza-Olivares F., Guerrero-Moncayo A., Chiong M., Castro P.F., García L., Gabrielli L., Corbalán R., Garrido-Olivares L., Lavandero S. VCAM-1 as a predictor biomarker in cardiovascular disease. Biochimica et Biophysica Acta (BBA). Molecular Basis of Disease. 2021; 1867(9): 166170. doi:10.1016/j.bbadis.2021.166170.

32. Belokopytova I.S., Moskaletz O.V., Paleev F.N., Zotova O.V. The diagnostic value of adhesive molecules sICAM-1 and sVCAM-1 in ischemic heart disease. Ateroskleroz i dislipidemii. 2013; 4: 62–5. (In Russian)

33. Chen Y.H., Lightman S., Eskandarpour M., Calder V.L. Adhesion Molecule Targeted Therapy for Non-Infectious Uveitis. International Journal of Molecular Sciences. 2022;23(1):503. doi:10.3390/ijms23010503.

34. Oates J.C., Russell D.L., Van Beusecum J.P. Endothelial cells: potential novel regulators of renal inflammation. American Journal of Physiology-Renal Physiology. 2022; 322(3): 309-F321. doi:10.1152/ajprenal.00371.2021.

35. Kong D.H., Kim Y.K., Kim M.R., Jang J.H., Lee S. Emerging Roles of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Immunological Disorders and Cancer. International journal of molecular sciences. 2018; 19(4): 1057. doi:10.3390/ijms19041057.

36. Fatahi S., Daneshzad E., Lotfi K., Azadbakht L. The effects of almond consumption on inflammatory biomarkers in adults: A systematic review and meta-analysis of randomized clinical trials. Advances in Nutrition. 2021:158. doi:10.1093/advances/nmab158.

37. Chen Y.T., Yuan H.X., Ou Z.J., Ou J.S. Microparticles (Exosomes) and Atherosclerosis. Current atherosclerosis reports. 2020; 22(6): 23. doi:10.1007/s11883-020-00841-z.

38. Lugo-Gavidia L. M., Burger D., Matthews V.B., Nolde J.M., Galindo Kiuchi M., Carnagarin R., Kannenkeril D., Chan J., Joyson A., Herat L.Y., Azzam O., Schlaich M.P. Role of microparticles in cardiovascular disease: implications for endothelial dysfunction, thrombosis, and inflammation. Hypertension. 2021; 77(6): 1825-1844. doi:10.1161/HYPERTENSIONAHA.121.16975.

39. Pernomian L., Moreira J.D., Gomes M.S. In the View of Endothelial Microparticles: Novel Perspectives for Diagnostic and Pharmacological Management of Cardiovascular Risk during Diabetes Distress. Journal of Diabetes Research. 2018; 2018. doi:10.1155/2018/9685205.

40. Rogula S., Gąsecka A., Filipiak K.J. Macroscopic role of microparticles in cardiovascular disease. Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego.2020; 49(286): 255-259.

41. Cooper S., Teoh H., Campeau M.A., Verma S., Leask R.L. Empagliflozin restores the integrity of the endothelial glycocalyx in vitro. Molecular and Cellular Biochemistry. 2019; 459: 121–130. doi: 10.1007/s11010-019-03555-2

42. Aini K., Fukuda D., Tanaka K., Higashikuni Y., Hirata Y., Yagi S., Kusunose K., Yamada H., Soeki T., Sata M. Vildagliptin, a DPP-4 Inhibitor, Attenuates Endothelial Dysfunction and Atherogenesis in Nondiabetic Apolipoprotein E-Deficient Mice. International heart journal. 2019; 60: 1421–1429. doi: 10.1536/ihj.19-117.

43. Sardu C., Paolisso P., Sacra C., Mauro C., Minicucci F., Portoghese M., Rizzo M.R., Barbieri M., Sasso F.C., D'Onofrio N., Balestrieri M.L., Calabrò P., Paolisso G., Marfella R. Effects of metformin therapy on coronary endothelial dysfunction in patients with prediabetes with stable angina and nonobstructive coronary artery stenosis: the CODYCE multicenter prospective study. Diabetes Care. 2019; 42(10): 1946-1955. doi: 10.2337/dc18-2356.

44. Becher T., Schulze T.J., Schmitt M., Trinkmann F., El-Battrawy I., Akin I., Kälsch T., Borggrefe M., Stach K. Ezetimibe inhibits platelet activation and uPAR expression on endothelial cells. International journal of cardiology. 2017; 227: 858–862. doi:10.1016/j.ijcard.2016.09.122.

45. Bacchiega B. C., Bacchiega A.B., Usnayo M.J., Bedirian R., Singh G., Pinheiro G.D. Interleukin 6 inhibition and coronary artery disease in a High‐Risk population: a prospective Community‐ Based clinical study. Journal of the American Heart Association. 2017; 6(3): e005038. doi:10.1161/JAHA.116.005038.

46. Ikonomidis I., Pavlidis G., Katsimbri P., Lambadiari V., Parissis J., Andreadou I., Tsoumani M., Boumpas D., Kouretas D., Iliodromitis E. Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19. Food and Chemical Toxicology. 2020; 145: 111694. doi:10.1016/j.fct.2020.111694.

47. Yang X., Wan M., Cheng Z., Wang Z., Wu Q. Tofacitinib inhibits ox-LDL-induced adhesion of THP-1 monocytes to endothelial cells. Artificial Cells, Nanomedicine, and Biotechnology. 2019; 47(1): 2775-2782. doi:10.1080/21691401.2 019.1573740.

48. Ashry N. A., Abdеlaziz R. R., Suddеk G. M. The potential effect of imatinib against hypercholesterolemia induced atherosclerosis, endothelial dysfunction and hepatic injury in rabbits. Life sciences. 2020; 243: 117275. doi:10.1016/j.lfs.2020.117275.

49. Zhou X., Cai J., Liu W., Wu X., Gao C. Cysteinyl leukotriene receptor type 1 (CysLT1R) antagonist zafirlukast protects against TNF-α-induced endothelial inflammation. Biomedicine & Pharmacotherapy. 2019; 111: 452-459. doi:10.1016/j.biopha.2018.12.064.

50. Pang J., Hu P., Wang J., Jiang J., Lai J. Vorapaxar stabilizes permeability of the endothelial barrier under cholesterol stimulation via the AKT/JNK and NF-κB signaling pathways. Molecular Medicine Reports. 2019; 19(6): 5291-5300. doi:10.3892/mmr.2019.10211.

51. Campo G., Vieceli Dalla Sega F., Pavasini R., Aquila G., Gallo F., Fortini F., Tonet E., Cimaglia P., Del Franco A., Pestelli G., Pecoraro A., Contoli M., Balla C., Biscaglia S., Rizzo P., Ferrari R. Biological effects of ticagrelor over clopidogrel in patients with stable coronary artery disease and chronic obstructive pulmonary disease. Thrombosis and haemostasis. 2017; 117(6): 1208-1216. doi:10.1160/TH16-12-0973.

52. Aquila G., Vieceli Dalla Sega F., Marracino L., Pavasini R., Cardelli L.S., Piredda A., Scoccia A., Martino V., Fortini F., Bononi I., Martini F., Manfrini M., Pannuti A., Ferrari R., Rizzo P., Campo G. Ticagrelor increases SIRT1 and HES1 mRNA levels in peripheral blood cells from patients with stable coronary artery disease and chronic obstructive pulmonary disease. International journal of molecular sciences. 2020; 21(5): 1576. doi:10.3390/ijms21051576.

53. Vianello F., Sambado L., Goss A., Fabris F., Prandoni P. Dabigatran antagonizes growth, cell‐cycle progression, migration, and endothelial tube formation induced by thrombin in breast and glioblastoma cell lines. Cancer Medicine. 2016; 5(10): 2886-2898. doi:10.1002/cam4.857

54. Pedralli M.L., Marschner R.A., Kollet D.P., Neto S.G., Eibel B., Tanaka H., Lehnen A.M. Different exercise training modalities produce similar endothelial function improvements in individuals with prehypertension or hypertension: A randomized clinical trial. Scientific reports. 2020; doi: 10: 1–9. 10.1038/s41598-020-64365-x

55. Fatima K., Rashid A.M., Memon U.A.A., Fatima S.S., Javaid S.S., Shahid O., Zehri F., Obaid M.A., Ahmad M., Almas T., Minhas A.M.K. Mediterranean Diet and its Effect on Endothelial Function: A Meta-analysis and Systematic Review. Irish Journal of Medical Science. 2022: 1-9. doi:10.1007/s11845-022-02944-9.

56. Golbidi S., Edvinsson L., Laher I. Smoking and Endothelial Dysfunction. Current Vascular Pharmacology. 2020;18(1):1-11. doi: 10.2174/1573403X14666180913120015.


Review

For citations:


Zakharyan E.A., Ageeva E.S., Shramko Yu.I., Malyi K.D., Gurtovaya A.K., Ibragimova R.E. A modern view on the diagnostic role of endothelial dysfunction biomarkers and the possibilities of its correction. Complex Issues of Cardiovascular Diseases. 2022;11(4S):194-207. (In Russ.) https://doi.org/10.17802/2306-1278-2022-11-4S-194-207

Views: 758


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2306-1278 (Print)
ISSN 2587-9537 (Online)