Advancing age is the major risk factor for the development of CVD (cardiovascular diseases). This is attributable, in part, to the development of vascular endothelial dysfunction, as indicated by reduced peripheral artery EDD (endothelium-dependent dilation) in response to chemical [typically ACh (acetylcholine)] or mechanical (intravascular shear) stimuli. Reduced bioavailability of the endothelium-synthesized dilating molecule NO (nitric oxide) as a result of oxidative stress is the key mechanism mediating reduced EDD with aging. Vascular oxidative stress increases with age as a consequence of greater production of reactive oxygen species (e.g. superoxide) without a compensatory increase in antioxidant defences. Sources of increased superoxide production include up-regulation of the oxidant enzyme NADPH oxidase, uncoupling of the normally NO-producing enzyme, eNOS (endothelial NO synthase) (due to reduced availability of the cofactor tetrahydrobiopterin) and increased mitochondrial synthesis during oxidative phosphorylation. Increased bioactivity of the potent endothelial-derived constricting factor ET-1 (endothelin-1), reduced endothelial production of/responsiveness to dilatory prostaglandins, the development of vascular inflammation, formation of AGEs (advanced glycation end-products), an increased rate of endothelial apoptosis and reduced expression of oestrogen receptor α (in postmenopausal females) also probably contribute to impaired EDD with aging. Several lifestyle and biological factors modulate vascular endothelial function with aging, including regular aerobic exercise, dietary factors (e.g. processed compared with non-processed foods), body weight/fatness, vitamin D status, menopause/oestrogen deficiency and a number of conventional and non-conventional risk factors for CVD. Given the number of older adults now and in the future, more information is needed on effective strategies for the prevention and treatment of vascular endothelial aging.

Abstract-We tested the hypothesis that vascular endothelial function, assessed by endothelium-dependent dilation, is related to serum vitamin D status among middle-aged and older adults without clinical disease, and that this is linked to inflammation. Brachial artery flow-mediated dilation, a measure of endothelium-dependent dilation, was lower (PϽ0. Key Words: aging Ⅲ endothelium-dependent dilation Ⅲ NFB Ⅲ interleukin-6 Ⅲ 1-␣ hydroxylase Ⅲ VDR C ardiovascular diseases (CVDs) remain the leading cause of death in modern societies, and advancing age is the major risk factor for CVD. [1][2][3] The increase in CVD risk with aging is attributable in large part to the development of vascular endothelial dysfunction, most commonly assessed as impaired endothelium-dependent dilation. 2,4,5 Consistent with this, middle-aged and older adults demonstrate reduced brachial artery flow-mediated dilation (FMD), a measure of endothelium-dependent dilation, 6 compared with young adults. 7 However, there is considerable variability in brachial artery FMD among middle-aged/older adults, and the contributing factors to impaired brachial FMD in this at-risk group are incompletely understood.Vitamin D deficiency is an independent predictor of CVD and all-cause mortality. 8 -10 Patients with chronic clinical diseases who are vitamin D deficient and young adults with severe vitamin D deficiency demonstrate impaired brachial artery FMD. [11][12][13] The physiological mechanisms by which vitamin D deficiency is linked to brachial artery FMD in these settings have not been established but may involve vascular inflammation. In humans, vitamin D deficiency is associated with increased circulating inflammatory proteins, 10,14,15 whereas in cultured vascular endothelial cells, vitamin D inhibits activation of the proinflammatory transcription factor nuclear factor B (NFB), 16 as well as the release of the inflammatory cytokine interleukin-6 (IL-6), 17 a downstream target of NFB activation. However, it is unknown whether vitamin D deficiency is associated with impaired brachial artery FMD among middle-aged/older adults without CVD and, if so, whether this is related to vascular inflammation.In the present study, we tested the hypothesis that brachial artery FMD is inversely related to vitamin D status (as reflected by serum concentrations of 25-hydroxyvitamin D