Vitamin D controls resistance artery function through regulation of perivascular adipose tissue hypoxia and inflammation.

Abstract

Vitamin D deficiency in human subjects is associated with hypertension, metabolic syndrome and related risk factors of cardiovascular diseases. Serum 25-hydroxyvitamin D levels correlate inversely with adiposity in obese and lean individuals. Bioactive vitamin D, or calcitriol, exerts anti-inflammatory effects on adipocytes, preadipocytes and macrophages in vitro. We tested the hypothesis that vitamin D deficiency alters the phenotype of perivascular adipose tissue (PVAT) leading to impaired function in resistance artery. To examine the effects of vitamin D and PVAT on vascular reactivity, myograph experiments were performed on arteries, with or without intact PVAT, from mice maintained on vitamin D-deficient, vitamin D-sufficient or vitamin D-supplemented diet. Systolic blood pressure was significantly increased in mice on vitamin D-deficient diet. Importantly, vitamin D deficiency enhanced angiotensin II-induced vasoconstriction and impaired the normal ability of PVAT to suppress contractile responses of the underlying mesenteric resistance artery to angiotensin II and serotonin. Furthermore, vitamin D deficiency caused upregulation of the mRNA expression of tumor necrosis factor-α, hypoxia-inducible factor-1α and its downstream target lysyl oxidase in mesenteric PVAT. Incubation of mesenteric arteries under hypoxic conditions impaired the anti-contractile effects of intact PVAT on those arteries from mice on vitamin D-sufficient diet. Vitamin D supplementation protected arteries against hypoxia-induced impairment of PVAT function. The protective effects of vitamin D against vascular dysfunction, hypertension and cardiovascular diseases may be mediated, at least in part, through regulation of inflammatory and hypoxia signaling pathways in PVAT.

• Authors: Christopher J Pelham, Elizabeth M Drews, Devendra K Agrawal
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 98 Pg. 1-10 (09 2016) ISSN: 1095-8584 [Electronic] England
• PMID: 27374117 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Vitamin D

Topics

• Adipose Tissue (metabolism)
• Animal Feed
• Animals
• Arteries (physiology)
• Blood Pressure
• Female
• Gene Expression Profiling
• Hypoxia (metabolism)
• Inflammation (metabolism)
• Male
• Mesenteric Arteries (physiology)
• Mice
• Muscle Contraction
• Phenotype
• Vascular Resistance
• Vitamin D (administration & dosage, metabolism)