events. Vitamin D and cardiovascular disease cardiovascular and Summary of vitamin D physiology Vitamin D (specifically vitamin D3, FGF-23 cholecalciferol) is synthesized in the skin hypertrophy. through the action of ultraviolet-B light on between to yield precholecalciferol, ventricular which spontaneously isomerises to left cholecalciferol. Ingestion of vitamin D3 or association LVH, vitamin D2 (ergocalciferol), found in dairy the cell; products, oily fish and eggs, is an additional source of circulating vitamin D. Hepatic muscle underlying hydroxylation of vitamin D3 and D2 yields vitamin D3 and D2 respectively, smooth pathways referred to collectively as 25(OH) vitamin D (25(OH)D). This circulating form of vitamin D is vascular possible readily measured and is considered to reflect of VSMC, the body’s vitamin D status (). However, 25(OH)D must undergo further hydroxylation Summary to 1,25-dihydroxyvitamin D (calcitriol) for 1.3 biological activity. This hydroxylation takes cardiovascular; CV, place primarily in cells of the renal proximal Figure tubule, catalysed by the mitochondrial enzyme 1-alpha hydroxylase. Calcitriol acts on the nuclear vitamin D receptor (VDR) to stimulate intestinal calcium and phosphate absorption, osteoclast activity, renal tubular phosphate reabsorption and to inhibit PTH synthesis. Together these actions maintain adequate blood levels of calcium and phosphate for bone formation. Regulation of circulating calcitriol concentrations occurs at the level of renal hydroxylase, the expression of which is inhibited by calcitriol and FGF-23, and
Figure 1.3 Summary of possible pathways underlying the association between FGF-23 and cardiovascular events. CV, cardiovascular; VSMC, vascular smooth muscle cell; LVH, left ventricular hypertrophy. Vitamin D and cardiovascular disease Summary of vitamin D physiology Vitamin D (specifically vitamin D3, cholecalciferol) is synthesized in the skin through the action of ultraviolet-B light on to yield precholecalciferol, which spontaneously isomerises to cholecalciferol. Ingestion of vitamin D3 or vitamin D2 (ergocalciferol), found in dairy products, oily fish and eggs, is an additional source of circulating vitamin D. Hepatic hydroxylation of vitamin D3 and D2 yields vitamin D3 and D2 respectively, referred to collectively as 25(OH) vitamin D (25(OH)D). This circulating form of vitamin D is readily measured and is considered to reflect the body’s vitamin D status (). However, 25(OH)D must undergo further hydroxylation to 1,25-dihydroxyvitamin D (calcitriol) for biological activity. This hydroxylation takes place primarily in cells of the renal proximal tubule, catalysed by the mitochondrial enzyme 1-alpha hydroxylase. Calcitriol acts on the nuclear vitamin D receptor (VDR) to stimulate intestinal calcium and phosphate absorption, osteoclast activity, renal tubular phosphate reabsorption and to inhibit PTH synthesis. Together these actions maintain adequate blood levels of calcium and phosphate for bone formation. Regulation of circulating calcitriol concentrations occurs at the level of renal hydroxylase, the expression of which is inhibited by calcitriol and FGF-23, and
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