Fliri Anton, Kajiji Shama
Emergent System Analytics LLC, Clinton, CT, United States.
Front Cardiovasc Med. 2024 Jun 25;11:1388025. doi: 10.3389/fcvm.2024.1388025. eCollection 2024.
Among the leading causes of natural death are cardiovascular diseases, cancer, and respiratory diseases. Factors causing illness include genetic predisposition, aging, stress, chronic inflammation, environmental factors, declining autophagy, and endocrine abnormalities including insufficient vitamin D levels. Inconclusive clinical outcomes of vitamin D supplements in cardiovascular diseases demonstrate the need to identify cause-effect relationships without bias. We employed a spectral clustering methodology capable of analyzing large diverse datasets for examining the role of vitamin D's genomic and non-genomic signaling in disease in this study. The results of this investigation showed the following: (1) vitamin D regulates multiple reciprocal feedback loops including p53, macrophage autophagy, nitric oxide, and redox-signaling; (2) these regulatory schemes are involved in over 2,000 diseases. Furthermore, the balance between genomic and non-genomic signaling by vitamin D affects autophagy regulation of macrophage polarization in tissue homeostasis. These findings provide a deeper understanding of how interactions between genomic and non-genomic signaling affect vitamin D pharmacology and offer opportunities for increasing the efficacy of vitamin D-centered treatment of cardiovascular disease and healthy lifespans.
自然死亡的主要原因包括心血管疾病、癌症和呼吸系统疾病。致病因素包括遗传易感性、衰老、压力、慢性炎症、环境因素、自噬能力下降以及包括维生素D水平不足在内的内分泌异常。维生素D补充剂在心血管疾病中临床结果尚无定论，这表明有必要无偏差地确定因果关系。在本研究中，我们采用了一种能够分析大量不同数据集的光谱聚类方法，以研究维生素D的基因组和非基因组信号在疾病中的作用。这项调查的结果如下：（1）维生素D调节多个相互反馈回路，包括p53、巨噬细胞自噬、一氧化氮和氧化还原信号；（2）这些调节机制涉及2000多种疾病。此外，维生素D在基因组和非基因组信号之间的平衡影响组织稳态中巨噬细胞极化的自噬调节。这些发现为深入理解基因组和非基因组信号之间的相互作用如何影响维生素D药理学提供了依据，并为提高以维生素D为中心的心血管疾病治疗效果和健康寿命提供了机会。
