Regulation of Acetylation States by Nutrients in the Inhibition of Vascular Inflammation and Atherosclerosis

Abstract

Atherosclerosis (AS) is a chronic metabolic disorder and primary cause of cardiovascular diseases, resulting in substantial morbidity and mortality worldwide. Initiated by endothelial cell stimulation, AS is characterized by arterial inflammation, lipid deposition, foam cell formation, and plaque development. Nutrients such as carotenoids, polyphenols, and vitamins can prevent the atherosclerotic process by modulating inflammation and metabolic disorders through the regulation of gene acetylation states mediated with histone deacetylases (HDACs). Nutrients can regulate AS-related epigenetic states via sirtuins (SIRTs) activation, specifically SIRT1 and SIRT3. Nutrient-driven alterations in the redox state and gene modulation in AS progression are linked to their protein deacetylating, anti-inflammatory, and antioxidant properties. Nutrients can also inhibit advanced oxidation protein product formation, reducing arterial intima-media thickness epigenetically. Nonetheless, knowledge gaps remain when it comes to understanding effective AS prevention through epigenetic regulation by nutrients. This work reviews and confirms the underlying mechanisms by which nutrients prevent arterial inflammation and AS, focusing on the epigenetic pathways that modify histones and non-histone proteins by regulating redox and acetylation states through HDACs such as SIRTs. These findings may serve as a foundation for developing potential therapeutic agents to prevent AS and cardiovascular diseases by employing nutrients based on epigenetic regulation.

Keywords: acetylation state; atherosclerosis; nutrients; vascular inflammation.

Figure 1

Role of nutrients in preventing atherosclerosis progression by epigenetic regulation of gene expression under dietary stress. Under dietary stress, HATs induce oxidative stress and inflammatory gene expression via epigenetic machinery. Nutrients serve as epigenetic regulators, reducing oxidative stress and repressing inflammatory gene expression through HDACs such as SIRT1 and SIRT3. Nutrients inhibit dietary-induced inflammation and metabolic dysfunctions in ECs, VSMCs, and macrophages, thereby preventing atherosclerosis progression.

Figure 2

Nutrient-mediated prevention of atherosclerosis by modulating redox and acetylation balance under inflammatory and abnormal metabolic conditions. Dietary stress contributes to histone acetylation by supplying acetyl groups, whereas nutrients facilitate deacetylation. An imbalance between these processes triggers pro-inflammatory gene expression and chronic inflammation. Dietary stress generates an excessive carbon source for the production of extra glucose and lipids, leading to increased carbon supply for histone acetylation and resulting in hyperglycemia and hyperlipidemia. On the other hand, nutrients regulate genes associated with glucose and lipid oxidation and maintain redox balance. Disruptions in glucose and lipid metabolism cause chronic metabolic dysfunction, but nutrients can modulate chronic inflammation and metabolic dysfunction to prevent atherosclerosis.