The impact of vitamin D deficiency and sex hormone imbalance on the cerebrovascular system
Nagy Dorina
Theoretical and Translational Medicine
Dr. Kellermayer Miklós
SE, Elméleti Orvostudományi Centrum, Hevesy György előadóterem
2024-05-10 10:00:00
The Mechanisms of Normal and Pathologic Functions of the Circulatory System
Dr. Benyó Zoltán
Pál Éva
Dr. Sára Levente
Dr. Menyhárt Ákos
Dr. Ács Nándor
Dr. Szekeres Mária
Dr. Tod Pál
Vitamin D deficiency represents an emerging cerebrovascular risk factor as it has been associated with the pathogenesis of cerebrovascular disorders, including ischemic stroke. Our previous findings showed the detrimental effects of vitamin D receptor (VDR) inactivity on the cerebrovascular function in male mice, characterized by more severe and prolonged blood flow reduction in the cerebral cortex after unilateral carotid artery occlusion (CAO) due to – at least partly – the altered morphology of leptomeningeal collaterals. To reveal if impaired extracranial collateral circulation also underlies the less efficient adaptation of VDR-mutant male mice, we examined the compensatory blood flow increase in the contralateral carotid artery, but we did not find any alterations in it. Nevertheless, the prevalence of cerebrovascular diseases might also be influenced by sex hormonal status, indicated by the heightened vulnerability of men, postmenopausal, and hyperandrogenic women compared to young, healthy women. Therefore, we aimed to investigate the interaction between vitamin D signaling and sex steroids in terms of cerebrovascular disorders by examining the impact of disrupted VDR signaling on the cerebrocortical microcirculation in intact, ovariectomized, and testosterone-treated female mice. Interestingly, unlike in males, disrupted vitamin D signaling by itself did not compromise the cerebrovascular adaptation to CAO in intact females, which might be attributed to the well-preserved leptomeningeal and extracranial collateral circulation. These findings strongly imply sex dimorphism in the effect of VDR inactivity on cerebrovascular function. Next, we investigated whether estrogen deficiency or hyperandrogenism aggravates the effect of VDR inactivity in females. Surprisingly, while ovariectomy did not undermine compensatory mechanisms following CAO, androgen excess combined with VDR inactivity resulted in prolonged hypoperfusion in the ipsilateral cerebral cortex. These findings suggest that the cerebrovascular consequences of disrupted VDR signaling are less pronounced in females, providing a level of protection even after ovariectomy. In contrast, even short-term androgen excess with the loss of VDR signaling may lead to unfavorable outcomes of cerebrovascular disorders, highlighting the complex interplay between androgens and vitamin D.
