title: 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.affiliation: Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Pelham
authors.affiliation: Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Drews
authors.affiliation: Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE 68178, USA. Electronic address: dkagr@creighton.edu.
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Agrawal
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000821:Animal Feed; D000818:Animals; D001158:Arteries / Q000502:physiology*; D001794:Blood Pressure; D005260:Female; D020869:Gene Expression Profiling; D000860:Hypoxia / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D051379:Mice; D009119:Muscle Contraction; D010641:Phenotype; D014655:Vascular Resistance; D014807:Vitamin D / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D014807:Vitamin D
keywords: Hypoxia; Inflammation; Perivascular adipose tissue; Resistance artery; Vitamin D