Methyl donor diet attenuates intimal hyperplasia after vascular injury in rats

Abstract

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.

Keywords: Extracellular matrix; Intimal hyperplasia; Methyl donor diet; Vascular remodeling.