Vitamin D deficiency causes inward hypertrophic remodeling and alters vascular reactivity of rat cerebral arterioles

PLOS ONE, Nov 2019

Background and purpose Vitamin D deficiency (VDD) is a global health problem, which can lead to several pathophysiological consequences including cardiovascular diseases. Its impact on the cerebrovascular system is not well understood. The goal of the present work was to examine the effects of VDD on the morphological, biomechanical and functional properties of cerebral arterioles. Methods Four-week-old male Wistar rats (n = 11 per group) were either fed with vitamin D deficient diet or received conventional rat chow with per os vitamin D supplementation. Cardiovascular parameters and hormone levels (testosterone, androstenedione, progesterone and 25-hydroxyvitamin D) were measured during the study. After 8 weeks of treatment anterior cerebral artery segments were prepared and their morphological, biomechanical and functional properties were examined using pressure microangiometry. Resorcin-fuchsin and smooth muscle actin staining were used to detect elastic fiber density and smooth muscle cell counts in the vessel wall, respectively. Sections were immunostained for eNOS and COX-2 as well. Results VDD markedly increased the wall thickness, the wall-to-lumen ratio and the wall cross-sectional area of arterioles as well as the number of smooth muscle cells in the tunica media. As a consequence, tangential wall stress was significantly lower in the VDD group. In addition, VDD increased the myogenic as well as the uridine 5’-triphosphate-induced tone and impaired bradykinin-induced relaxation. Decreased eNOS and increased COX-2 expression were also observed in the endothelium of VDD animals. Conclusions VDD causes inward hypertrophic remodeling due to vascular smooth muscle cell proliferation and enhances the vessel tone probably because of increased vasoconstrictor prostanoid levels in young adult rats. In addition, the decreased eNOS expression results in endothelial dysfunction. These morphological and functional alterations can potentially compromise the cerebral circulation and lead to cerebrovascular disorders in VDD.

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Vitamin D deficiency causes inward hypertrophic remodeling and alters vascular reactivity of rat cerebral arterioles

February Vitamin D deficiency causes inward hypertrophic remodeling and alters vascular reactivity of rat cerebral arterioles E?va Pa? l 0 Leila Hadjadj 0 Zolta? n Fonta? nyi Anna Monori-Kiss 0 Zsuzsanna Mezei Norbert Lippai Attila Magyar Andrea Heinzlmann Gelle? rt Karvaly Emil Monos 0 Gyo? rgy Na? dasy Zolta? n Benyo? 0 Szabolcs Va? rb??ro? 0 Institute of Clinical Experimental Research, Semmelweis University , Budapest, Hungary, 2 2 Background and purpose Vitamin D deficiency (VDD) is a global health problem, which can lead to several pathophysiological consequences including cardiovascular diseases. Its impact on the cerebrovascular system is not well understood. The goal of the present work was to examine the effects of VDD on the morphological, biomechanical and functional properties of cerebral arterioles. Data Availability Statement; All relevant data are within the paper - Editor: Alain-Pierre Gadeau, "INSERM", FRANCE Methods Four-week-old male Wistar rats (n = 11 per group) were either fed with vitamin D deficient diet or received conventional rat chow with per os vitamin D supplementation. Cardiovascular parameters and hormone levels (testosterone, androstenedione, progesterone and 25hydroxyvitamin D) were measured during the study. After 8 weeks of treatment anterior cerebral artery segments were prepared and their morphological, biomechanical and functional properties were examined using pressure microangiometry. Resorcin-fuchsin and smooth muscle actin staining were used to detect elastic fiber density and smooth muscle cell counts in the vessel wall, respectively. Sections were immunostained for eNOS and COX-2 as well. Results VDD markedly increased the wall thickness, the wall-to-lumen ratio and the wall cross-sectional area of arterioles as well as the number of smooth muscle cells in the tunica media. As a consequence, tangential wall stress was significantly lower in the VDD group. In addition, VDD increased the myogenic as well as the uridine 5'-triphosphate-induced tone and impaired bradykinin-induced relaxation. Decreased eNOS and increased COX-2 expression were also observed in the endothelium of VDD animals. data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Conclusions VDD causes inward hypertrophic remodeling due to vascular smooth muscle cell proliferation and enhances the vessel tone probably because of increased vasoconstrictor prostanoid levels in young adult rats. In addition, the decreased eNOS expression results in endothelial dysfunction. These morphological and functional alterations can potentially compromise the cerebral circulation and lead to cerebrovascular disorders in VDD. Introduction Vitamin D deficiency (VDD) or insufficiency affects 1 billion people from all age groups worldwide. In addition to its well-characterized roles in calcium and phosphate homeostasis as well as in bone metabolism, 1,25-dihydroxyvitamin D?the active metabolite of vitamin D (VitD)?has numerous biological actions [ 1 ]. Besides interacting with the intracellular VitD receptor and regulating the expression of up to 200 genes, it mediates non-genomic actions as well [ 2 ]. VDD is associated with an increased risk of malignant tumor formation, autoimmune and infectious diseases as well as depression [ 1 ]. Diabetes mellitus and metabolic syndrome are also linked to VDD, as 1,25-dihydroxyvitamin D improves ?-cell function and insulin sensitivity [ 3 ]. There is a growing body of evidence linking VDD to cardiovascular diseases including hypertension, atherosclerosis and coronary artery disease. Furthermore, a direct impact of VDD on endothelial dysfunction, arterial stiffness and vascular inflammation was also reported [ 2, 4, 5 ]. The effects of VDD on the cerebrovascular system are as yet less understood, although several studies highlight the importance of sufficient VitD status in cerebrovascular health. Low concentrations of VitD are associated with an increased risk of cerebrovascular diseases including ischemic stroke [6?9] and with poor poststroke outcome [ 10 ]. In addition, VDD is linked to chronic brain injury associated with cerebral small vessel disease [ 11 ]. The effect of VitD status on stroke severity was confirmed in rodent models as well: the infarction volume was larger and more severe poststroke behaviour impairment was observed in VitD-deficient rats as compared to VitD-sufficient ones [ 12 ]. In the present study, we hypothesized that the aforementioned adverse effects of VDD in stroke are related?at least in part?to VDD-induced alterations in cerebral arterioles. Therefore, we aimed to analyze the changes in the morphological, biomechanical and functional properties of the anterior cerebral artery (ACA) in a rodent model of VDD. Materials and methods Animals All procedures conformed to the Guide for the Care and Use of Labo (...truncated)


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Éva Pál, Leila Hadjadj, Zoltán Fontányi, Anna Monori-Kiss, Zsuzsanna Mezei, Norbert Lippai, Attila Magyar, Andrea Heinzlmann, Gellért Karvaly, Emil Monos, György Nádasy, Zoltán Benyó, Szabolcs Várbíró. Vitamin D deficiency causes inward hypertrophic remodeling and alters vascular reactivity of rat cerebral arterioles, PLOS ONE, 2018, Volume 13, Issue 2, DOI: 10.1371/journal.pone.0192480