Role of Vitamin D in Atherosclerosis

Abstract

A therosclerosis, the principal cause of cardiovascular diseases (CVDs), is a process that involves a complex interplay among different factors and cell types, including cells of the immune system (T cells, B cells, natural killer cells, monocytes/macrophages, dendritic cells) and cells of the vessel wall (endothelial cells [ECs], vascular smooth muscle cells [VSMCs]). The atherogenic process evolves in different stages, starting from inflammatory endothelial activation/ dysfunction and resulting in plaque vulnerability and rupture. Vitamin D deficiency affects almost 50% of the population worldwide. It has been suggested that this pandemic might contribute to the worldwide increased prevalence of CVD. 9-11Several mechanisms have been proposed to account for this inverse relationship. In addition to its effects exerted on numerous tissues and organs that indirectly participate in the atherosclerosis, vitamin D is directly involved in this systemic inflammatory process.12,13 Vitamin D receptors (VDRs) are present in all cells implicated in atherosclerosis, including ECs, VSMCs, and immune cells. Vitamin D appears to regulate a wide range of physiological and pathological processes like vascular cell growth, migration, and differentiation; immune response modulation; cytokine expression; and inflammatory and fibrotic pathways, all of which play a crucial role, starting from the early stage of endothelial activation/dysfunction to the later stages of the plaque vulnerability and rupture.In this review, we provide current data on the effects of vitamin D on cells directly implicated in atherosclerosis such as ECs, VSMCs, and immune cells (lymphocytes, monocytes, macrophages, etc) with a focus on the underlying molecular mechanisms, which are still largely unknown. We also summarize reports related to the favorable (antiatherogenic) actions of vitamin D in tissues and organs that indirectly participate in the atherogenic process. Finally, we critically discuss clinical studies to assess the protective role of vitamin D and the efficacy of vitamin D and VDR agonists in CVD. Because a comprehensive background is a prerequisite for further discussions of vitamin D-induced effects, we provide a brief description of vitamin D metabolism and mechanism of action. Vitamin D Metabolism and Mechanism of ActionVitamin D is a steroid hormone that comes in 2 forms that differ chemically in their side chain, D 2 and D 3 (Figure 1). Either produced in the skin (D 3 ) from 7-dehydrocholesterol by exposure to ultraviolet-B light or ingested with foods of plant or animal origin (D 2 and D 3 , respectively), vitamin D is biologically inert and requires 2 hydroxylations to form its active metabolite. 10 The first hydroxylation is constitutive and takes place in the liver by vitamin D-25-hydroxylase to form 25(OH)D. The second hydroxylation is catalyzed by 25(OH) D-1aOHase (CYP27B1) to form the biologically active form of vitamin D, 1,25(OH) 2 D (calcitriol; see Figure 1). This latter 1a-hydroxylation of 25(OH)D takes place in most tiss...

Impact of vitamin D supplementation on endothelial and inflammatory markers in adults: A systematic review

“…Kassi et al [44] suggested that a principal contributory factor to endothelial dysfunction is the diminished availability of NO, and the rise in the production of free radicals. Hence, the proposed direct mechanism by which vitamin D may improve endothelial function may be by enhancing nitric oxide production and decreasing the production of free radicals.…”

Deficiencia de vitamina D y su asociación con enfermedad arterial coronaria en población mexicana: estudio Genético de la Enfermedad Aterosclerosa

“…Estos resultados contrastan con estudios que han mostrado que los valores bajos de VD se asocian a un estado inflamatorio sistémico, favorecen la resistencia a la insulina y activan el sistema renina-angiotensina-aldosterona, con la subsecuente elevación de la presión arterial y la hipertrofia del músculo cardiaco y de las células musculares lisas [28][29][30] . En concordancia con estos hallazgos, varios estudios observacionales han reportado una asociación entre la deficiencia de 25(OH)D y la presencia de EAC clínica 13,31-33 y subclínica [34][35][36][37][38] .…”

Possible Pivotal Role of Latent Chronic T. gondii Infection in the Pathogenesis of Atherosclerosis

“…processes characteristic for atherosclerosis, including vascular cell growth, migration, and differentiation, immune response modulation, cytokine expression, and inflammatory and fibrotic pathways [762] . Vitamin D deficiency is affecting more than one billion people to approximately 50% of population worldwide [762][763][764] .…”

“…Vitamin D deficiency is affecting more than one billion people to approximately 50% of population worldwide [762][763][764] . Shortage of vitamin D induced atherosclerosis and high blood pressure in mice [765] .…”

“…Shortage of vitamin D induced atherosclerosis and high blood pressure in mice [765] . Epidemiological and clinical evidence linked vitamin D deficiency to cardiovascular diseases in humans [766] , including carotid atherosclerosis [762,767,768] . Vitamin D receptor (VDR) is present in all cells implicated with atherosclerosis, such as endothelial cells, vascular smooth muscle cells, and immune cells [762] .…”