Vitamin D and Osteogenic Differentiation in the Artery Wall

Hsu, Jeffrey J.; Tintut, Yin; Demer, Linda L.

doi:10.2215/cjn.01220308

Cited by 51 publications

(34 citation statements)

References 62 publications

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“…Protective dosages of 1,25(OH)D suppressed aortic osteoblastic gene expression, which is normally increased in CKD, suggesting a mechanism for this inhibition of aortic calcification. In addition, evidence suggested that Wnt signaling may modulate vascular calcification via osteoblastic differentiation of vascular smooth muscle cells, reinforcing the role of osteoblast regulation in vascular calcification (47,48). The relationship between vitamin D and vascular health is reinforced at a clinical level by Melamed et al, who reported an 80% increase in the adjusted prevalence of peripheral artery disease among NHANES participants with the lowest quartile of 25(OH)D (Ͻ17.8 ng/ml) in comparison with those in the highest quartile (Ն29.2 ng/ml) (49).…”

Section: Vitamin D and Vascular Healthmentioning

confidence: 80%

Vitamin D and the Cardiovascular System

Artaza

Mehrotra

Norris

2009

Clinical Journal of the American Society of Nephrology

170

132

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Several epidemiologic and clinical studies have suggested that there is a strong association between hypovitaminosis D and cardiovascular disease (CVD). Hypovitaminosis D was reported as a risk factor for increased cardiovascular events among 1739 adult participants in the Framingham Offspring Study. Analysis of more than 13,000 adults in the Third National Health and Nutrition Examination Survey (NHANES III) showed that even though hypovitaminosis D is associated with an increased prevalence of CVD risk factors, its association with all-cause mortality is independent of these risk factors. Importantly, epidemiologic studies suggested that patients who had chronic kidney disease and were treated with activated vitamin D had a survival advantage when compared with those who did not receive treatment with these agents. Mechanistically, emerging data have linked vitamin D administration with improved cardiac function and reduced proteinuria, and hypovitaminosis D is associated with obesity, insulin resistance, and systemic inflammation. Preliminary studies suggested that activated vitamin D inhibits the proliferation of cardiomyoblasts by promoting cell-cycle arrest and enhances the formation of cardiomyotubes without inducing apoptosis. Activated vitamin D has also been shown to attenuate left ventricular dysfunction in animal models and humans. In summary, emerging studies suggest that hypovitaminosis D has emerged as an independent risk factor for all-cause and cardiovascular mortality, reinforcing its importance as a public health problem. There is a need to advance our understanding of the biologic pathways through which vitamin D affects cardiovascular health and to conduct prospective clinical interventions to define precisely the cardioprotective effects of nutritional vitamin D repletion. There is increasing evidence that the kidney is not unique in its ability to convert 25(OH)D to 1,25(OH)D, It was recently demonstrated that many tissues not only express the VDR but also possess 25(OH)D-1␣-hydroxylase activity. The role of this paracrine production of 1,25(OH)D in these tissues is not well understood, but a variety of in vitro studies indicated that this process may be involved in a wide range of physiologic functions, including regulation of cytokines, inflammatory and/or fibrotic pathways, the renin-angiotensin system, vascular and cardiac cell function, immune response modulation, cell growth and differentiation, and others (7-15). Several of the biologic pathways through which the effects of 1,25(OH)D are mediated remain poorly understood but may account for its role in cardiovascular health (Figure 1).

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Section: Vitamin D and Vascular Healthmentioning

confidence: 80%

Vitamin D and the Cardiovascular System

Artaza

Mehrotra

Norris

2009

Clinical Journal of the American Society of Nephrology

170

132

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“…65 Various proteins involved in osteogenesis have been detected in VSMCs and atherosclerotic lesions such as osteopontin, bone morphogenetic protein-2 and matrix Gla protein, fetuin-A, osteoprotegerin, and receptor activator of NF-κB ligand, playing either a stimulatory or an inhibitory role in the calcification process. 66 Data on the role of vitamin D in the vascular calcification are conflicting. In vitro experiments support that VSMCs undergo calcification when treated with 1a,25(OH) 2 D through several mechanisms.…”

Section: Effects Of Vitamin D On Vsmcsmentioning

confidence: 99%

Role of Vitamin D in Atherosclerosis

et al. 2013

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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...

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“…Active vitamin D also increases calcium uptake in aortic smooth muscles, although this finding is not true in all tissues. However, in humans clinical studies show an inverse association between vascular calcification and 1,25(OH)2D3 (28). Thus, increased vascular calcium content may partly explain the inverse association of vascular stiffness with 25(OH)D3 and 1,25(OH)2D3 manifested by increased pulse wave velocity and blunted flow-mediated dilation (29).…”

Section: Vitamin D Ultraviolet (Uvb) Light and Bpmentioning

confidence: 99%

Vitamin D, Blood Pressure, and African Americans

Rostand¹

2010

Clinical Journal of the American Society of Nephrology

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Vitamin D deficiency has increasingly been recognized in the general population and especially in African Americans whose deep skin pigmentation makes vitamin D photosynthesis inefficient. Over the last decade there has been increasing interest in the role that vitamin D deficiency may play in BP modulation because many epidemiologic studies have shown an inverse association between serum vitamin D concentration and BP. There is a high prevalence of vitamin D deficiency in African Americans who also have an increased susceptibility to develop hypertension and its consequences. This paper will review the circumstances leading to vitamin D deficiency in the African American population and will also discuss how vitamin D deficiency can affect the renin-angiotensin system, free radical production, inflammatory processes, and carbohydrate tolerance that in turn influence vascular endothelial function and vascular structure producing increased vascular resistance. It will speculate that the presence of vitamin D deficiency throughout life from its earliest phases may adversely affect the microvasculature in African Americans, thereby playing a major role in the genesis and maintenance of hypertension.

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Vitamin D and Osteogenic Differentiation in the Artery Wall

Cited by 51 publications

References 62 publications

Vitamin D and the Cardiovascular System

Vitamin D and the Cardiovascular System

Role of Vitamin D in Atherosclerosis

Vitamin D, Blood Pressure, and African Americans

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