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

Christopher J. Pelham, Elizabeth M. Drews, Devendra K. Agrawal

    Research output: Contribution to journalArticlepeer-review

    17 Scopus citations

    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.

    Original languageEnglish
    Pages (from-to)1-10
    Number of pages10
    JournalJournal of Molecular and Cellular Cardiology
    Volume98
    DOIs
    StatePublished - Sep 1 2016

    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Cardiology and Cardiovascular Medicine

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