Department of Clinical Nutrition, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Key Laboratory of Medical Electrophysiology, Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease/Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China.
J Nutr Biochem. 2024 Jan;123:109486. doi: 10.1016/j.jnutbio.2023.109486. Epub 2023 Oct 14.
Environmental factors, particularly dietary habits, play an important role in cardiovascular disease susceptibility and progression through epigenetic modification. Previous studies have shown that hyperplastic vascular intima after endarterectomy is characterized by genome-wide hypomethylation. The purpose of this study was to investigate whether methyl donor diet affects intimal hyperplasia and the possible mechanisms involved. Intimal hyperplasia was induced in SD rats by carotid artery balloon injury. From 8 d before surgery to 28 d after surgery, the animals were fed a normal diet (ND) or a methyl donor diet (MD) supplemented with folic acid, vitamin B12, choline, betaine, and zinc. Carotid artery intimal hyperplasia was observed by histology, the effect of MD on carotid protein expression was analyzed by proteomics, functional clustering, signaling pathway, and upstream-downstream relationship of differentially expressed proteins were analyzed by bioinformatics. Results showed that MD attenuated balloon injury-induced intimal hyperplasia in rat carotid arteries. Proteomic analysis showed that there were many differentially expressed proteins in the common carotid arteries of rats fed with two different diets. The differentially expressed proteins are mainly related to the composition and function of the extracellular matrix (EMC), and changes in the EMC can lead to vascular remodeling by affecting fibrosis and stiffness of the blood vessel wall. Changes in the levels of vasculotropic proteins such as S100A9, ILF3, Serpinh1, Fbln5, LOX, HSPG2, and Fmod may be the reason why MD attenuates intimal hyperplasia. Supplementation with methyl donor nutrients may be a beneficial measure to prevent pathological vascular remodeling after injury.
环境因素，特别是饮食习惯，通过表观遗传修饰在心血管疾病易感性和进展中起重要作用。先前的研究表明，血管内膜切除术后的增生性血管内膜表现为全基因组低甲基化。本研究旨在探讨供甲基饮食是否影响内膜增生及其可能涉及的机制。通过颈动脉球囊损伤诱导 SD 大鼠发生内膜增生。从术前 8 天到术后 28 天，动物分别给予正常饮食（ND）或补充叶酸、维生素 B12、胆碱、甜菜碱和锌的供甲基饮食（MD）。通过组织学观察颈动脉内膜增生，蛋白质组学分析 MD 对颈动脉蛋白表达的影响，采用生物信息学分析差异表达蛋白的功能聚类、信号通路以及上下游关系。结果表明，MD 可减轻大鼠颈动脉球囊损伤诱导的内膜增生。蛋白质组学分析表明，两种不同饮食喂养的大鼠颈总动脉有许多差异表达蛋白。差异表达蛋白主要与细胞外基质（EMC）的组成和功能有关，EMC 的变化可通过影响血管壁纤维化和僵硬导致血管重塑。S100A9、ILF3、Serpinh1、Fbln5、LOX、HSPG2 和 Fmod 等血管生成蛋白水平的变化可能是 MD 减轻内膜增生的原因。补充供甲基营养物质可能是预防损伤后病理性血管重塑的有益措施。
