Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, Italy.
Cardiology and Cardiovascular Physiopathology, Azienda Ospedaliero-Universitaria S. Maria della Misericordia, 06156 Perugia, Italy.
Life Sci. 2022 Jan 15;289:120193. doi: 10.1016/j.lfs.2021.120193. Epub 2021 Dec 3.
Vitamin D is a hormone with both genomic and non-genomic actions. It exerts its activity by binding vitamin D receptor (VDR), which belongs to the superfamily of nuclear receptors and ligand-activated transcription factors. Since VDR has been found in various tissues, it has been estimated that it regulates approximately 3% of the human genome. Several recent studies have shown pleiotropic effects of vitamin D in various processes such as cellular proliferation, differentiation, DNA repair and apoptosis and its involvement in different pathophysiological conditions as inflammation, diabetes mellitus, and anemia. It has been suggested that vitamin D could play an important role in neurodegenerative and cardiovascular disorders. Moderate to strong associations between lower serum vitamin D concentrations and stroke and cardiovascular events have been identified in different analytic approaches, even after controlling for traditional demographic and lifestyle covariates. The mechanisms behind the associations between vitamin D and cerebrovascular and cardiologic profiles have been widely examined both in animal and human studies. Optimization of vitamin D levels in human subjects may improve insulin sensitivity and beta-cell function and lower levels of inflammatory markers. Moreover, it has been demonstrated that altered gene expression of VDR and 1,25D3-membrane-associated rapid response steroid-binding (1,25D3-MARRS) receptor influences the role of vitamin D within neurons and allows them to be more prone to degeneration. This review summarizes the current understanding of the molecular mechanisms underlying vitamin D signaling and the consequences of vitamin D deficiency in neurodegenerative and cardiovascular disorders.
维生素 D 是一种具有基因组和非基因组作用的激素。它通过与维生素 D 受体 (VDR) 结合来发挥其活性，VDR 属于核受体和配体激活转录因子的超家族。由于 VDR 已在各种组织中被发现，据估计它可以调节人类基因组的大约 3%。最近的几项研究表明，维生素 D 在细胞增殖、分化、DNA 修复和细胞凋亡等多种过程中具有多效性作用，并且参与了炎症、糖尿病和贫血等不同的病理生理状况。有人认为维生素 D 在神经退行性和心血管疾病中可能发挥重要作用。不同分析方法表明，血清维生素 D 浓度较低与中风和心血管事件之间存在中度至高度关联，即使在控制了传统的人口统计学和生活方式协变量后也是如此。在动物和人类研究中，广泛研究了维生素 D 与脑血管和心脏特征之间的关联背后的机制。优化人体中的维生素 D 水平可能会改善胰岛素敏感性和β细胞功能，并降低炎症标志物的水平。此外，已经证明 VDR 和 1,25D3-膜相关快速反应类固醇结合 (1,25D3-MARRS) 受体的基因表达改变会影响维生素 D 在神经元中的作用，并使它们更容易发生退化。这篇综述总结了目前对维生素 D 信号转导的分子机制以及维生素 D 缺乏在神经退行性和心血管疾病中的后果的理解。
