Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk 630090, Russia.
The Natural Sciences Department, Novosibirsk State University, Novosibirsk 630090, Russia.
Int J Mol Sci. 2023 May 19;24(10):9010. doi: 10.3390/ijms24109010.
Atherosclerosis is a systemic disease in which focal lesions in arteries promote the build-up of lipoproteins and cholesterol they are transporting. The development of atheroma (atherogenesis) narrows blood vessels, reduces the blood supply and leads to cardiovascular diseases. According to the World Health Organization (WHO), cardiovascular diseases are the leading cause of death, which has been especially boosted since the COVID-19 pandemic. There is a variety of contributors to atherosclerosis, including lifestyle factors and genetic predisposition. Antioxidant diets and recreational exercises act as atheroprotectors and can retard atherogenesis. The search for molecular markers of atherogenesis and atheroprotection for predictive, preventive and personalized medicine appears to be the most promising direction for the study of atherosclerosis. In this work, we have analyzed 1068 human genes associated with atherogenesis, atherosclerosis and atheroprotection. The hub genes regulating these processes have been found to be the most ancient. In silico analysis of all 5112 SNPs in their promoters has revealed 330 candidate SNP markers, which statistically significantly change the affinity of the TATA-binding protein (TBP) for these promoters. These molecular markers have made us confident that natural selection acts against underexpression of the hub genes for atherogenesis, atherosclerosis and atheroprotection. At the same time, upregulation of the one for atheroprotection promotes human health.
动脉粥样硬化是一种全身性疾病,其动脉中的局灶性病变会促进脂蛋白和它们所运输的胆固醇的积累。动脉粥样硬化斑块(动脉粥样硬化形成)的发展会使血管变窄,减少血液供应,导致心血管疾病。根据世界卫生组织(WHO)的数据,心血管疾病是导致死亡的主要原因,尤其是在 COVID-19 大流行之后,这一情况更为严重。动脉粥样硬化的形成有多种因素,包括生活方式因素和遗传易感性。抗氧化饮食和娱乐性运动可以作为动脉粥样硬化的保护因子,减缓动脉粥样硬化形成。寻找动脉粥样硬化形成和动脉粥样硬化保护的分子标志物,用于预测、预防和个体化医学,似乎是动脉粥样硬化研究最有前途的方向。在这项工作中,我们分析了与动脉粥样硬化形成、动脉粥样硬化和动脉粥样硬化保护相关的 1068 个人类基因。调控这些过程的枢纽基因被发现是最古老的。对其启动子中所有 5112 个 SNP 的计算机分析揭示了 330 个候选 SNP 标记,这些标记在统计学上显著改变了 TATA 结合蛋白(TBP)与这些启动子的亲和力。这些分子标记使我们有信心,自然选择会对抗动脉粥样硬化形成、动脉粥样硬化和动脉粥样硬化保护的枢纽基因表达不足。同时,上调与动脉粥样硬化保护相关的基因会促进人类健康。