Angiogenesis, Inflammation & Therapeutics | Online ISSN  2207-872X
REVIEWS   (Open Access)

Vitamin D Deficiency As A Contributor To Atherosclerosis Development – A Review

Anastasia V. Poznyak 1*, Victoria A. Khotina 2, Alexandra A. Melnichenko 2, Victor Y Glanz 2, Vasily N. Sukhorukov 2, and Alexander N. Orekhov 2*

+ Author Affiliations

Journal of Angiotherapy 8(2) 1-11 https://doi.org/10.25163/angiotherapy.829389

Submitted: 26 November 2023  Revised: 13 January 2024  Published: 05 February 2024 

Abstract

Vitamin D, obtained from food or synthesized in the skin through sun exposure, plays a vital role in various physiological processes. This review focuses on cholecalciferol (vitamin D3), specifically its production from 7-dehydrocholesterol in the skin. The aim is to evaluate the impact of vitamin D on the development of atherosclerosis and other pathological conditions. Atherosclerosis, a chronic vascular inflammation caused by innate immunity, is of particular interest. Understanding the role of vitamin D in reducing inflammation and oxidative stress holds significant implications for effective treatment strategies. Deficiency of vitamin D has been observed in individuals with cardiovascular disease, ischemic stroke, and myocardial infarction. Hypovitaminosis D is also suspected to contribute to vascular calcification, a factor closely associated with cardiovascular morbidity and mortality. Investigating the multifaceted effects of vitamin D on various pathophysiological processes is thus crucial.

Keywords:  Atherosclerosis; Vitamin D; Nutrition.

References

Abe, R. J., Abe, J. I., Nguyen, M. T. H., Olmsted-Davis, E. A., Mamun, A., Banerjee, P., Cooke, J. P., Fang, L., Pownall, H., & Le, N. T. (2022). Free Cholesterol Bioavailability and Atherosclerosis. Current atherosclerosis reports, 24(5), 323–336. https://doi.org/10.1007/s11883-022-01011-z

Amrein, K., Scherkl, M., Hoffmann, M., Neuwersch-Sommeregger, S., Köstenberger, M., Tmava Berisha, A., Martucci, G., Pilz, S., & Malle, O. (2020). Vitamin D deficiency 2.0: an update on the current status worldwide. European journal of clin-ical nutrition, 74(11), 1498–1513. https://doi.org/10.1038/s41430-020-0558-y

Anastasia V. Poznyak, Ludmila V Nedosugova, Vasily N. Sukhorukov. (2023a). Hepatitis C and atherosclerosis: inflammatory interplay, Journal of Angiotherpay, 7(1), 1-10, 9361

Anastasia V. Poznyak, Varvara A. Orekhova, Vasily N. Sukhorukov. (2024c). Platelet Implication in Atherosclerosis Pathogenesis, Journal of Angiotherapy, 8(1), 1-8, 9385

Anastasia V. Poznyak, Victoria A. Khotina, Vasily N. Sukhorukov et al., (2024b). Maternal hypercholesterolemia is a significant risk factor for atherogenesis – A Systematic Review, Journal of Angiotherapy, 8(1), 1-10, 9390

Anastasia V. Poznyak, Victoria A. Khotina, Vasily N. Sukhorukov et al., (2024a). Two Forms of C-Reactive Protein and Their Implication for Atherogenesis: Focus on Monomeric Form, Journal of Angiotherapy, 8(1), 1-12, 9386

Anastasia V. Poznyak, Victoria A. Khotina, Mikhail. Popov, Alexander D. Zhuravlev, Vasily N. Sukhorukov, and Alexander N. Orekhov, (2023b), The way of cholesterol in atherogenesis: from the main enemy to complex biomarkers, Journal of Angiotherpay, 7(1), 1-7

Becker, L. E., Koleganova, N., Piecha, G., Noronha, I. L., Zeier, M., Geldyyev, A., Kökeny, G., Ritz, E., & Gross, M. L. (2011). Effect of paricalcitol and calcitriol on aortic wall remodeling in uninephrectomized ApoE knockout mice. American jour-nal of physiology. Renal physiology, 300(3), F772–F782. https://doi.org/10.1152/ajprenal.00042.2010

Bilinski, W. J., Szternel, L., Siodmiak, J., Paradowski, P. T., Domagalski, K., & Sypniewska, G. (2021). Low Serum 25-hydroxyvitamin D Level Does Not Adversely Affect Bone Turnover in Prepubertal Children. Nutrients, 13(10), 3324. https://doi.org/10.3390/nu13103324

Brøndum-Jacobsen, P., Benn, M., Afzal, S., & Nordestgaard, B. G. (2015). No evidence that genetically reduced 25-hydroxyvitamin D is associated with increased risk of ischaemic heart disease or myocardial infarction: a Mendelian randomization study. International journal of epidemiology, 44(2), 651–661. https://doi.org/10.1093/ije/dyv078

Calton, E. K., Keane, K. N., Newsholme, P., & Soares, M. J. (2015). The Impact of Vitamin D Levels on Inflammatory Sta-tus: A Systematic Review of Immune Cell Studies. PloS one, 10(11), e0141770. https://doi.org/10.1371/journal.pone.0141770

Christodoulou, S., Goula, T., Ververidis, A., & Drosos, G. (2013). Vitamin D and bone disease. BioMed research interna-tional, 2013, 396541. https://doi.org/10.1155/2013/396541

Courbebaisse, M., & Lanske, B. (2018). Biology of Fibroblast Growth Factor 23: From Physiology to Pathology. Cold Spring Harbor perspectives in medicine, 8(5), a031260. https://doi.org/10.1101/cshperspect.a031260

Das, J. K., Salam, R. A., Mahmood, S. B., Moin, A., Kumar, R., Mukhtar, K., Lassi, Z. S., & Bhutta, Z. A. (2019). Food fortifi-cation with multiple micronutrients: impact on health outcomes in general population. The Cochrane database of system-atic reviews, 12(12), CD011400. https://doi.org/10.1002/14651858.CD011400.pub2

de Brito Galvao, J. F., Nagode, L. A., Schenck, P. A., & Chew, D. J. (2013). Calcitriol, calcidiol, parathyroid hormone, and fibroblast growth factor-23 interactions in chronic kidney disease. Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001), 23(2), 134–162. https://doi.org/10.1111/vec.12036

de la Guía-Galipienso, F., Martínez-Ferran, M., Vallecillo, N., Lavie, C. J., Sanchis-Gomar, F., & Pareja-Galeano, H. (2021). Vitamin D and cardiovascular health. Clinical nutrition (Edinburgh, Scotland), 40(5), 2946–2957. https://doi.org/10.1016/j.clnu.2020.12.025

De Martinis, M., Allegra, A., Sirufo, M. M., Tonacci, A., Pioggia, G., Raggiunti, M., Ginaldi, L., & Gangemi, S. (2021). Vita-min D Deficiency, Osteoporosis and Effect on Autoimmune Diseases and Hematopoiesis: A Review. International journal of molecular sciences, 22(16), 8855. https://doi.org/10.3390/ijms22168855

Di Liberto, D., Scazzone, C., La Rocca, G., Cipriani, P., Lo Pizzo, M., Ruscitti, P., Agnello, L., Ciaccio, M., Dieli, F., Giaco-melli, R., Triolo, G., Ciccia, F., Sireci, G., & Guggino, G. (2019). Vitamin D increases the production of IL-10 by regulatory T cells in patients with systemic sclerosis. Clinical and experimental rheumatology, 37 Suppl 119(4), 76–81.

Dibaba D. T. (2019). Effect of vitamin D supplementation on serum lipid profiles: a systematic review and me-ta-analysis. Nutrition reviews, 77(12), 890–902. https://doi.org/10.1093/nutrit/nuz037

Dominguez, L. J., Farruggia, M., Veronese, N., & Barbagallo, M. (2021). Vitamin D Sources, Metabolism, and Deficiency: Available Compounds and Guidelines for Its Treatment. Metabolites, 11(4), 255. https://doi.org/10.3390/metabo11040255

Dominguez, L., Veronese, N., & Barbagallo, M. (2020). Magnesium and Hypertension in Old Age. Nutrients, 13(1), 139. https://doi.org/10.3390/nu13010139

Dube, P., DeRiso, A., Patel, M., Battepati, D., Khatib-Shahidi, B., Sharma, H., Gupta, R., Malhotra, D., Dworkin, L., Haller, S., & Kennedy, D. (2021). Vascular Calcification in Chronic Kidney Disease: Diversity in the Vessel Wall. Biomedicines, 9(4), 404. https://doi.org/10.3390/biomedicines9040404

Durham, A. L., Speer, M. Y., Scatena, M., Giachelli, C. M., & Shanahan, C. M. (2018). Role of smooth muscle cells in vascu-lar calcification: implications in atherosclerosis and arterial stiffness. Cardiovascular research, 114(4), 590–600. https://doi.org/10.1093/cvr/cvy010

Dziedzic, E. A., Gasior, J. S., Sowinska, I., Dabrowski, M., & Jankowski, P. (2022). Vitamin D Level in Patients with Consec-utive Acute Coronary Syndrome Is Not Correlated with the Parameters of Platelet Activity. Journal of clinical medi-cine, 11(3), 707. https://doi.org/10.3390/jcm11030707

Ewendt, F., Feger, M., & Föller, M. (2021). Role of Fibroblast Growth Factor 23 (FGF23) and αKlotho in Cancer. Frontiers in cell and developmental biology, 8, 601006. https://doi.org/10.3389/fcell.2020.601006

Filgueiras, M. S., Rocha, N. P., Novaes, J. F., & Bressan, J. (2020). Vitamin D status, oxidative stress, and inflammation in children and adolescents: A systematic review. Critical reviews in food science and nutrition, 60(4), 660–669. https://doi.org/10.1080/10408398.2018.1546671

Fleet J. C. (2017). The role of vitamin D in the endocrinology controlling calcium homeostasis. Molecular and cellular endocrinology, 453, 36–45. https://doi.org/10.1016/j.mce.2017.04.008

Gondim, F., Caribé, A., Vasconcelos, K. F., Segundo, A. D., & Bandeira, F. (2016). Vitamin D Deficiency Is Associated with Severity of Acute Coronary Syndrome in Patients with Type 2 Diabetes and High Rates of Sun Exposure. Clinical medicine insights. Endocrinology and diabetes, 9, 37–41. https://doi.org/10.4137/CMED.S39427

Göring H. (2018). Vitamin D in Nature: A Product of Synthesis and/or Degradation of Cell Membrane Compo-nents. Biochemistry. Biokhimiia, 83(11), 1350–1357. https://doi.org/10.1134/S0006297918110056

Grant, A. M., Avenell, A., Campbell, M. K., McDonald, A. M., MacLennan, G. S., McPherson, G. C., Anderson, F. H., Cooper, C., Francis, R. M., Donaldson, C., Gillespie, W. J., Robinson, C. M., Torgerson, D. J., Wallace, W. A., & RECORD Trial Group (2005). Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet (London, England), 365(9471), 1621–1628. https://doi.org/10.1016/S0140-6736(05)63013-9

Harahap, I. A., Landrier, J. F., & Suliburska, J. (2022). Interrelationship between Vitamin D and Calcium in Obesity and Its Comorbid Conditions. Nutrients, 14(15), 3187. https://doi.org/10.3390/nu14153187

Hiemstra, T. F., Lim, K., Thadhani, R., & Manson, J. E. (2019). Vitamin D and Atherosclerotic Cardiovascular Disease. The Journal of clinical endocrinology and metabolism, 104(9), 4033–4050. https://doi.org/10.1210/jc.2019-00194

Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium, Ross, A. C., Tay-lor, C. L., Yaktine, A. L., & Del Valle, H. B. (Eds.). (2011). Dietary Reference Intakes for Calcium and Vitamin D. National Academies Press (US).

Irving, A. A., Plum, L. A., Blaser, W. J., Ford, M. R., Weng, C., Clipson, L., DeLuca, H. F., & Dove, W. F. (2015). Cholecal-ciferol or 25-hydroxycholecalciferol neither prevents nor treats adenomas in a rat model of familial colon cancer. The Journal of nutrition, 145(2), 291–298. https://doi.org/10.3945/jn.114.204396

Keung, L., & Perwad, F. (2018). Vitamin D and kidney disease. Bone reports, 9, 93–100. https://doi.org/10.1016/j.bonr.2018.07.002

Legarth, C., Grimm, D., Krüger, M., Infanger, M., & Wehland, M. (2019). Potential Beneficial Effects of Vitamin D in Coronary Artery Disease. Nutrients, 12(1), 99. https://doi.org/10.3390/nu12010099

Lehmann B. (2009). Role of the vitamin D3 pathway in healthy and diseased skin--facts, contradictions and hypothe-ses. Experimental dermatology, 18(2), 97–108. https://doi.org/10.1111/j.1600-0625.2008.00810.x

Linton, M. F., Yancey, P. G., Davies, S. S., Jerome, W. G., Linton, E. F., Song, W. L., Doran, A. C., & Vickers, K. C. (2019). The Role of Lipids and Lipoproteins in Atherosclerosis. In K. R. Feingold (Eds.) et. al., Endotext. MDText.com, Inc.

Mandarino, N. R., Júnior, F.d, Salgado, J. V., Lages, J. S., & Filho, N. S. (2015). Is vitamin d deficiency a new risk factor for cardiovascular disease?. The open cardiovascular medicine journal, 9, 40–49. https://doi.org/10.2174/1874192401509010040

Miao, C. Y., Fang, X. J., Chen, Y., & Zhang, Q. (2020). Effect of vitamin D supplementation on polycystic ovary syndrome: A meta-analysis. Experimental and therapeutic medicine, 19(4), 2641–2649. https://doi.org/10.3892/etm.2020.8525

Milutinovic, A., Šuput, D., & Zorc-Pleskovic, R. (2020). Pathogenesis of atherosclerosis in the tunica intima, media, and adventitia of coronary arteries: An updated review. Bosnian journal of basic medical sciences, 20(1), 21–30. https://doi.org/10.17305/bjbms.2019.4320

Morvaridzadeh, M., Agah, S., Alibakhshi, P., Heydari, H., Hoseini, A. S., Palmowski, A., Toupchian, O., Abdollahi, S., Re-zamand, G., & Heshmati, J. (2021). Effects of Calcium and Vitamin D Co-supplementation on the Lipid Profile: A Sys-tematic Review and Meta-analysis. Clinical therapeutics, 43(9), 274–296. https://doi.org/10.1016/j.clinthera.2021.07.018

Mousa, H., Islam, N., Ganji, V., & Zughaier, S. M. (2020). Serum 25-Hydroxyvitamin D Is Inversely Associated with Mon-ocyte Percentage to HDL Cholesterol Ratio among Young Healthy Adults in Qatar. Nutrients, 13(1), 127. https://doi.org/10.3390/nu13010127

Nnakenyi, I. D., Agbo, E. O., Nnakenyi, E. F., & Wakwe, V. C. (2022). A reference interval study of serum 25-Hydroxyvitamin D among an African elderly population. African health sciences, 22(4), 220–228. https://doi.org/10.4314/ahs.v22i4.27

Pérez, L. M., Pareja-Galeano, H., Sanchis-Gomar, F., Emanuele, E., Lucia, A., & Gálvez, B. G. (2016). 'Adipaging': ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue. The Journal of physiology, 594(12), 3187–3207. https://doi.org/10.1113/JP271691

Pilz, S., Trummer, C., Theiler-Schwetz, V., Grübler, M. R., Verheyen, N. D., Odler, B., Karras, S. N., Zittermann, A., & März, W. (2022). Critical Appraisal of Large Vitamin D Randomized Controlled Trials. Nutrients, 14(2), 303. https://doi.org/10.3390/nu14020303

Plominski, J., Grzybowski, R., Fiedorowicz, E., Sienkiewicz-Szlapka, E., Rozmus, D., Król-Grzymala, A., Jarmolowska, B., Kordulewska, N., & Cieslinska, A. (2022). Vitamin D Metabolic Pathway Components in Orthopedic Patientes-Systematic Review. International journal of molecular sciences, 23(24), 15556. https://doi.org/10.3390/ijms232415556

Prentice, R. L., Howard, B. V., Van Horn, L., Neuhouser, M. L., Anderson, G. L., Tinker, L. F., Lampe, J. W., Raftery, D., Pettinger, M., Aragaki, A. K., Thomson, C. A., Mossavar-Rahmani, Y., Stefanick, M. L., Cauley, J. A., Rossouw, J. E., Man-son, J. E., & Chlebowski, R. T. (2021). Nutritional epidemiology and the Women's Health Initiative: a review. The Ameri-can journal of clinical nutrition, 113(5), 1083–1092. https://doi.org/10.1093/ajcn/nqab091

Ramasamy I. (2020). Vitamin D Metabolism and Guidelines for Vitamin D Supplementation. The Clinical biochemist. Reviews, 41(3), 103–126. https://doi.org/10.33176/AACB-20-00006

Santoro, D., Caccamo, D., Lucisano, S., Buemi, M., Sebekova, K., Teta, D., & De Nicola, L. (2015). Interplay of vitamin D, erythropoiesis, and the renin-angiotensin system. BioMed research international, 2015, 145828. https://doi.org/10.1155/2015/145828

Scragg, R., Stewart, A. W., Waayer, D., Lawes, C. M. M., Toop, L., Sluyter, J., Murphy, J., Khaw, K. T., & Camargo, C. A., Jr (2017). Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assess-ment Study : A Randomized Clinical Trial. JAMA cardiology, 2(6), 608–616. https://doi.org/10.1001/jamacardio.2017.0175

Sen, A., Vincent, V., Thakkar, H., Abraham, R., & Ramakrishnan, L. (2022). Beneficial Role of Vitamin D on Endothelial Progenitor Cells (EPCs) in Cardiovascular Diseases. Journal of lipid and atherosclerosis, 11(3), 229–249. https://doi.org/10.12997/jla.2022.11.3.229

Silva, F. M., Pesaro, A. E., Franken, M., & Wajngarten, M. (2015). Acute management of unstable angina and non-ST seg-ment elevation myocardial infarction. Einstein (Sao Paulo, Brazil), 13(3), 454–461. https://doi.org/10.1590/S1679-45082015RW3172

Surdu, A. M., Pînzariu, O., Ciobanu, D. M., Negru, A. G., Cainap, S. S., Lazea, C., Iacob, D., Saraci, G., Tirinescu, D., Borda, I. M., & Cismaru, G. (2021). Vitamin D and Its Role in the Lipid Metabolism and the Development of Atherosclero-sis. Biomedicines, 9(2), 172. https://doi.org/10.3390/biomedicines9020172

Szymczak-Pajor, I., Drzewoski, J., & Sliwinska, A. (2020). The Molecular Mechanisms by Which Vitamin D Prevents Insu-lin Resistance and Associated Disorders. International journal of molecular sciences, 21(18), 6644. https://doi.org/10.3390/ijms21186644

Tukaj C. (2008). Enhanced proliferation of aortal smooth muscle cells treated by 1,25(OH)2D3 in vitro coincides with impaired formation of elastic fibres. International journal of experimental pathology, 89(2), 117–124. https://doi.org/10.1111/j.1365-2613.2008.00578.x

Voortman, T., van den Hooven, E. H., Heijboer, A. C., Hofman, A., Jaddoe, V. W., & Franco, O. H. (2015). Vitamin D defi-ciency in school-age children is associated with sociodemographic and lifestyle factors. The Journal of nutrition, 145(4), 791–798. https://doi.org/10.3945/jn.114.208280

Wajda, J., Swiat, M., Owczarek, A. J., Brzozowska, A., Olszanecka-Glinianowicz, M., & Chudek, J. (2019). Severity of Vita-min D Deficiency Predicts Mortality in Ischemic Stroke Patients. Disease markers, 2019, 3652894. https://doi.org/10.1155/2019/3652894

Wang, H., Xia, N., Yang, Y., & Peng, D. Q. (2012). Influence of vitamin D supplementation on plasma lipid profiles: a me-ta-analysis of randomized controlled trials. Lipids in health and disease, 11, 42. https://doi.org/10.1186/1476-511X-11-42

Wu-Wong J. R. (2009). Potential for vitamin D receptor agonists in the treatment of cardiovascular disease. British journal of pharmacology, 158(2), 395–412. https://doi.org/10.1111/j.1476-5381.2009.00171.x

Zito, C., Manganaro, R., Carerj, S., Antonini-Canterin, F., & Benedetto, F. (2020). Peripheral Artery Disease and Stroke. Journal of cardiovascular echography, 30(Suppl 1), S17–S25. https://doi.org/10.4103/jcecho.jcecho_4_19

PDF
Full Text
Export Citation

View Dimensions


View Plumx



View Altmetric



38
Save
0
Citation
525
View
0
Share