Lipoproteins and Their Receptors Association in Cerebrovascular Disease Pathogenesis: A Comprehensive Analysis

Nargiza Maksudovna Vakhabova ¹, Maksud Makhmudovich Asadullaev ², Gulnara Sattarovna Raximbayeva ³, Nigina Akram qizi Botirova, ⁴ Aktamov Shohruhbek Ulug’bek ug’li ⁵

This study showed critical biomarkers' roles in cerebrovascular accidents, offering insights into therapeutic strategies for stroke prevention and management.

Abstract

Atherosclerosis, a leading cause of cardiovascular and cerebrovascular diseases, is driven by dyslipidemia and inflammatory processes. This study aimed to assess the relationship between lipoproteins and their receptors in patients with acute cerebrovascular accidents, using Receiver Operating Characteristic (ROC) analysis to evaluate their predictive value for stroke risk. A total of 165 patients with acute cerebrovascular events were included, and comprehensive assessments, including enzyme immunoassays for lipoprotein A (Lp(a)) and lipoprotein-associated phospholipase A2 (Lp-PLA2), were conducted. Results revealed significant associations between lipoprotein levels and neurological deficits, with a 2.3-fold increase in Lp(a) and a 2.2-fold decrease in low-density lipoprotein receptors (LDLR) in severe cases. Elevated lectin-like oxidized LDL receptor (LOX-1) and Lp-PLA2 levels were also noted, highlighting their roles in plaque destabilization and inflammation. The findings underscore the complex interplay of lipid metabolism, thrombus formation, and endothelial dysfunction in cerebrovascular events. This study emphasizes the importance of early detection and targeted interventions to modulate lipoprotein levels and reduce inflammation, offering potential strategies to mitigate stroke risk in atherosclerosis patients.

Keywords: Atherosclerosis, Lipoprotein(a), Low-Density Lipoprotein Receptors, Stroke Pathogenesis, Inflammatory Markers

References

Amit, V. K., & Kathiresan, S. (2016). Lipoprotein(a): Physiological and pathophysiological perspectives. Trends in Endocrinology & Metabolism, 27(6), 364-375.

Arabidze, G. G. (2018). Immunology of atherosclerosis: Modern achievements and prospects. Therapist, (12), 4-25.

Arun, S. (2008). High-sensitivity C-reactive protein and cardiovascular disease: A resolute belief or an elusive link? Circulation, 118(20), 2089-2097.

Benjamin, E. J., Blaha, M. J., Chiuve, S. E., Cushman, M., Das, S. R., Deo, R., ... & Muntner, P. (2019). Heart disease and stroke statistics—2019 update: A report from the American Heart Association. Circulation, 139(10), e56-e528.

Berberich, A. J., & Hegele, R. A. (2019). Dyslipidemia: Genetic aspects. In Oxford Textbook of Endocrinology and Diabetes (pp. 579-586). Oxford University Press.

Brown, M. S., & Goldstein, J. L. (2009). A receptor-mediated pathway for cholesterol homeostasis. Science, 232(4746), 34-47.

Conrad, A., & Bartenschlager, R. (2013). Viral hepatitis: Mechanisms of viral persistence and a path to a cure. Nature Reviews Gastroenterology & Hepatology, 10(12), 743-755.

Dekker, J. M., et al. (2010). The role of lipoprotein-associated phospholipase A2 in cardiovascular disease. Journal of Clinical Lipidology, 4(4), 293-300.

Hayashida, K., et al. (2013). LOX-1: A potential therapeutic target for vascular disorders. Journal of Molecular and Cellular Cardiology, 66, 103-110.

Herz, J., et al. (1987). LDL receptor-mediated endocytosis: Concepts emerging from familial hypercholesterolemia. Science, 235(4796), 680-685.

Hsue, P. Y., et al. (2015). Cardiovascular disease in HIV-infected patients. Journal of the American College of Cardiology, 65(8), 830-839.

Jayaraman, S., et al. (1999). Prognostic value of lipoprotein-associated phospholipase A2 in cardiovascular disease. New England Journal of Medicine, 341(1), 19-26.

Khera, A. V., & Kathiresan, S. (2016). Lipoprotein(a) and its role in atherosclerosis: A comprehensive review. Circulation Research, 119(7), 1049-1062.

Klimchuk, A. V., & Kozlov, V. A. (2021). Atherosclerosis: Pathogenetic mechanisms and prospects for correction. Bulletin of Experimental Biology and Medicine, 171(5), 597-600.

Klimov, A. N., et al. (2003). Pathogenesis and pathogenetic mechanisms of atherosclerosis. Advances in Cardiovascular Diseases, 44(4), 345-355.

Libby, P., et al. (2005). Inflammation and atherosclerosis: From the endothelium to the plaque. Journal of the American College of Cardiology, 46(1), C7-C19.

Libby, P., et al. (2010). Inflammation and its role in human disease. Nature, 473(7347), 333-342.

Libby, P., et al. (2019). Atherosclerosis: A multifactorial disease. Cell, 179(2), 283-297.

Monami, M., et al. (2019). PCSK9 inhibitors and cardiovascular outcomes: A meta-analysis of randomized clinical trials. Journal of the American Heart Association, 8(10), e012924.

Musunuru, K., & Kathiresan, S. (2016). Genetics of coronary artery disease. Annual Review of Genomics and Human Genetics, 17, 377-410.

Nelson, R. H. (2013). Hyperlipidemia as a risk factor for cardiovascular disease. Primary Care: Clinics in Office Practice, 40(1), 195-211.

Nikolic, D., et al. (2011). Lipoprotein-associated phospholipase A2 and cardiovascular risk. Current Medicinal Chemistry, 18(12), 1762-1771.

Nordestgaard, B. G. (2010). Atherosclerosis and lipoprotein metabolism: New insights. European Heart Journal, 31(24), 2983-2991.

Prudnikov, A. V., & Shchupakova, N. A. (2018). Autoimmune mechanisms of atherosclerosis. Autoimmunity Reviews, 17(5), 533-539.

Roden, M., et al. (2016). Mechanisms of lipoprotein(a) in atherosclerosis. European Heart Journal, 37(15), 1175-1182.

Rohatgi, A. (2011). HDL cholesterol efflux capacity and cardiovascular disease. New England Journal of Medicine, 364(2), 127-135.

Shimano, H. (2009). SREBP: A mediator of cholesterol metabolism. Journal of Lipid Research, 50(Suppl), S120-S125.

Virani, S. S., et al. (2016). Lipoprotein(a) as a cardiovascular risk factor: Current understanding and future directions. Journal of the American College of Cardiology, 68(22), 2395-2402.

Wang, N., et al. (2018). Mechanisms of LDL receptor regulation. Annual Review of Biochemistry, 87, 789-817.

Weber, C., & Ley, K. (2014). Pathogenesis of atherosclerosis. Journal of Internal Medicine, 276(2), 114-126.

Williams, K. J., & Krauss, R. M. (2017). Hyperlipidemia and cardiovascular risk: Mechanisms and interventions. Journal of Clinical Endocrinology & Metabolism, 102(11), 3936-3944.

Zakrzewska, K. E., & Czarna, A. (2021). Genetics and molecular biology of LDL receptor. Journal of Human Genetics, 66(7), 647-661.