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25-Hydroxyvitamin D deficiency is associated with inflammation-linked vascular endothelial dysfunction in middle-aged and older adults.

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 (P<0.01) in vitamin D-insufficient (3.7 ± 0.2%; serum 25-hydroxyvitamin D [25(OH)D]: 20 to 29 ng/mL; 62 ± 1 years of age; n = 31; mean± SE) and vitamin D-deficient (3.2 ± 0.3%; 25(OH)D: <20 ng/mL; 63 ± 2 years of age; n = 22) versus vitamin D-sufficient (4.6 ± 0.4%; 25(OH)D: >29 ng/mL; 61 ± 1 years of age; n = 22) subjects, whereas endothelium-independent dilation (brachial dilation to sublingual nitroglycerine) did not differ (P = 0.45). Among all subjects, brachial flow-mediated dilation was positively related to serum 25(OH)D (%?: r = 0.35; P<0.01) but not 1,25-dihydroxyvitamin D (r = -0.06; P = 0.61), the active form of vitamin D. Vascular endothelial cell expression of the proinflammatory transcription factor nuclear factor ?B was greater in deficient versus sufficient subjects (0.59 ± 0.07 versus 0.44 ± 0.05; P<0.05), and inhibition of nuclear factor ?B (4 days oral salsalate) improved flow-mediated dilation to a greater extent in subjects with lower versus higher 25(OH)D (+3.7 ± 0.6 versus +2.0 ± 0.2%; P<0.05). Endothelial cell expression of the downstream proinflammatory cytokine interleukin-6 also was higher in deficient versus sufficient subjects (0.67 ± 0.08 versus 0.47 ± 0.05; P<0.01) and inversely related to serum 25(OH)D level (r = -0.62; P<0.01), whereas vitamin D receptor and 1-? hydroxylase, the 25(OH)D to 1,25-dihydroxyvitamin D converting enzyme, were lower (P<0.05). Inadequate serum 25(OH)D is associated with vascular endothelial dysfunction among healthy middle-aged/older adults, and this is mediated in part by nuclear factor ?B-related inflammation. Reduced vitamin D receptor and 1-? hydroxylase may be molecular mechanisms linking vitamin D insufficiency to endothelial dysfunction.

SUBMITTER: Jablonski KL

PROVIDER: S-EPMC3020150 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Project description:ObjectivesThis study sought to determine the efficacy of dietary sodium restriction (DSR) for improving vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure (SBP) (130-159 mm Hg) and the associated physiological mechanisms.BackgroundVascular endothelial dysfunction develops with advancing age and elevated SBP, contributing to increased cardiovascular risk. DSR lowers BP, but its effect on vascular endothelial function and mechanisms involved are unknown.MethodsSeventeen subjects (11 men and 6 women; mean age, 62 ± 7 years) completed a, randomized crossover study of 4 weeks of both low (DSR) and normal sodium intake. Vascular endothelial function (endothelium-dependent dilation; EDD), nitric oxide (NO)/tetrahydrobiopterin (BH(4)) bioavailability, and oxidative stress-associated mechanisms were assessed following each condition.ResultsUrinary sodium excretion was reduced by ≈ 50% (to 70 ± 30 mmol/day), and conduit (brachial artery flow-mediated dilation [FMD(BA)]) and resistance (forearm blood flow responses to acetylcholine [FBF(ACh)]) artery EDD were 68% and 42% (peak FBF(ACh)) higher following DSR (p < 0.005). Low sodium markedly enhanced NO-mediated EDD (greater ΔFBF(ACh) with endothelial NO synthase inhibition) without changing endothelial NO synthase expression/activation (Ser 1177 phosphorylation), restored BH(4) bioactivity (less ΔFMD(BA) with acute BH(4)), abolished tonic superoxide suppression of EDD (less ΔFMD(BA) and ΔFBF(ACh) with ascorbic acid infusion), and increased circulating superoxide dismutase activity (all p < 0.05). These effects were independent of ΔSBP. Other subject characteristics/dietary factors and endothelium-independent dilation were unchanged.ConclusionsDSR largely reversed both macro- and microvascular endothelial dysfunction by enhancing NO and BH(4) bioavailability and reducing oxidative stress. Our findings support the emerging concept that DSR induces "vascular protection" beyond that attributable to its BP-lowering effects.

Project description:BackgroundHong Kong faces several public health problems including malnutrition and osteoporosis. Considering the typical Chinese diet and overall low physical activity levels of Chinese adults, timely interventions to improve nutritional status and bone health are needed.ObjectivesWe examined the effects of a nutrition plus exercise intervention on serum vitamin B-12 and 25-hydroxyvitamin D [25(OH)D], bone turnover markers, and parathyroid hormone (PTH) concentrations in apparently healthy Chinese middle-aged and older adults.MethodsIn this 24-wk randomized controlled trial, 180 Chinese adults (85 women, mean ± SD age: 61 ± 6 y) were randomly assigned to receive a fortified milk supplement (2 × 30 g/d) and an exercise program (2 × 1 h/wk including resistance, balance, and aerobic training) or no intervention. The primary outcome was physical performance. In this article we analyzed the secondary outcomes serum vitamin B-12 and 25(OH)D concentrations, assessed at baseline, 12 wk, and 24 wk. Also, bone turnover markers and PTH concentrations were studied. Linear mixed models evaluated group differences over time.ResultsA significant time × group interaction (P < 0.001) was found for serum vitamin B-12 and 25(OH)D concentrations and the bone turnover markers, but not for serum PTH concentrations (P = 0.09). The intervention increased mean ± SD vitamin B-12 concentrations from baseline (345 ± 119 pmol/L) to 24 wk (484 ± 136 pmol/L), whereas concentrations remained stable within the control. For 25(OH)D concentrations, the intervention group had a greater increase from baseline (54.7 ± 14.2 nmol/L) to 24 wk (80.1 ± 19.2 nmol/L) than the control (60.6 ± 15.2 compared with 65.6 ± 14.6 nmol/L). The ratio of the net effect of bone formation and resorption was greater in the intervention group, suggesting less bone remodeling, irrespective of sex.ConclusionsA fortified milk supplement and exercise intervention successfully improved vitamin B-12 and 25(OH)D concentrations as well as the balance of bone turnover markers of Chinese middle-aged and older adults.This trial was registered at trialregister.nl as NTR6214.

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25-Hydroxyvitamin D deficiency is associated with inflammation-linked vascular endothelial dysfunction in middle-aged and older adults.

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