Vitamin D Deficiency and the Risk of Cerebrovascular Disease

Abstract

Vitamin D deficiency has been clearly linked to major chronic diseases associated with oxidative stress, inflammation, and aging, including cardiovascular and neurodegenerative diseases, diabetes, and cancer. In particular, the cardiovascular system appears to be highly sensitive to vitamin D deficiency, as this may result in endothelial dysfunction and vascular defects via multiple mechanisms. Accordingly, recent research developments have led to the proposal that pharmacological interventions targeting either vitamin D deficiency or its key downstream effects, including defective autophagy and abnormal pro-oxidant and pro-inflammatory responses, may be able to limit the onset and severity of major cerebrovascular diseases, such as stroke and cerebrovascular malformations. Here we review the available evidence supporting the role of vitamin D in preventing or limiting the development of these cerebrovascular diseases, which are leading causes of disability and death all over the world.

Protein kinase Cα regulates the nucleocytoplasmic shuttling of KRIT1

“…Since its original discovery as a novel interactor of the small GTPase Rap1 ( Serebriiskii et al, 1997 ), as well as being the major protein involved in the pathogenesis of the human genetic disease CCM ( Laberge-le Couteulx et al, 1999 ; Sahoo et al, 1999 ), KRIT1 has progressively emerged as a key player in fundamental cellular functions, including control of cell–matrix and cell–cell adhesion ( Glading et al, 2007 ; Zhang et al, 2001 ), Rho GTPase activity and actin cytoskeleton dynamics ( Stockton et al, 2010 ), intracellular redox homeostasis and signaling ( Antognelli et al, 2018a , b ; Cianfruglia et al, 2019 ; Goitre et al, 2010 , 2014 ), and autophagy ( Marchi et al, 2015 ). The pleiotropic functions of KRIT1 have been clearly implicated in the maintenance of endothelial cell homeostasis and blood-brain barrier integrity through the control of coordinated molecular and cellular responses to oxidative stress and inflammation, which in turn suggest novel mechanisms of CCM disease onset and severity, providing new preventive and therapeutic perspectives ( Antognelli et al, 2020 ; Choquet et al, 2016 ; De Luca et al, 2018 ; Finetti et al, 2020 ; Gibson et al, 2015 ; Goitre et al, 2017 ; Kim et al, 2020 ; Marchi et al, 2016 ; Perrelli et al, 2018 ; Retta and Glading, 2016 ; Trapani and Retta, 2015 ). On the other hand, recent evidence demonstrates that the consequences of KRIT1 loss-of-function mutations extend beyond the pathogenesis of CCM disease, being also implicated in the development of aortic endothelial dysfunction and atherosclerosis ( Vieceli Dalla Sega et al, 2019 ), as well as of epithelial barrier dysfunction in the gastrointestinal tract ( Wei et al, 2020 ).…”

Inflammatory syndromes including PIMS-TS in children hospitalised in the Malopolska region of Poland in the first wave of the COVID-19 pandemic

“…Amongst irregularities found in laboratory tests, attention should be drawn to a low vitamin D 3 concentration (9.3 ng/ml IGR 30-50) in a patient with a severe course of PIMS-TS and a confirmed SARS-CoV-2 infection. There is vast evidence that vitamin D deficiency may lead to endothelial dysfunction and pathological changes in the vascular system [24], which is of significance in the pathogenesis of KD and may be a potential risk factor for a more severe course of COVID-19 [25], as in the case reported above.…”

Both cardiovascular and cerebrovascular events are decreased following long‐term narrowband ultraviolet B phototherapy in patients with vitiligo: a propensity score matching analysis

“…Another potential mechanism of the protective phototherapy on cardiovascular system includes vitamin D. Phototherapy is known to increase serum concentration of 25(OH)D3 37–39 . Vitamin D deficiency may result in enhanced susceptibility of cardiovascular diseases via pro‐oxidant and pro‐inflammatory mechanisms, and have an influence on endothelial function and arterial thrombogenesis 40,41 . However, there are controversies of the association between vitamin D and cardiovascular diseases.…”