Dietary compounds have potential in controlling atherosclerosis by modulating macrophage cholesterol metabolism and inflammation via miRNA

Abstract

Atherosclerosis (AS) is a typical example of a widespread fatal cardiovascular disease. Accumulation of cholesterol-laden macrophages in the artery wall forms the starting point of AS. Increased influx of oxidized low-density lipoprotein to macrophages and decreased efflux of free cholesterol out of macrophages constitute major factors promoting the development of AS. Inflammation further aggravates the development of AS along or via interaction with the cholesterol metabolism. Many microRNAs (miRNAs) are related to the regulation of macrophage in AS in aspects of cholesterol metabolism and inflammation signaling. Dietary compounds perform AS inhibitory effects via miRNAs in the cholesterol metabolism (miR-19b, miR-378, miR-10b, miR-33a, and miR-33b) and two miRNAs in the inflammation signaling (miR-155 and miR-146a). The targeted miRNAs in the cholesterol metabolism vary greatly among different food compounds; however, in inflammation signaling, most food compounds target miR-155. Many receptors are involved in macrophages via miRNAs, including ABCA1 and ABCG1 as major receptors in the cholesterol metabolism, while nuclear factor-κB (NF-κB) and Nrf2 signaling and PI3K/AKT signaling pathways are targeted during inflammation. This article reviews current literature to investigate possible AS therapy with dietary compounds via targeting miRNAs. Currently existing problems were also discussed to guide further studies.

Keywords: Cardiovascular diseases; Nutrition.

Fig. 1

Roles of monocytes/macrophages in promoting AS and the influence of dietary compounds on macrophages. At the initiation of AS, the damage of the endothelium, which is to a certain extent caused by the accumulation of modified cholesterol (ox-LDL), initiates an immune response recruiting monocytes into the subendothelial space, where these cells differentiate into macrophages. The formed macrophages tend to uptake the ox-LDL unlimitedly and become cholesterol-loaded foam cells. These foam cells accumulate to create fatty streaks, which form the central feature of the early stage during the development of atherosclerotic lesions. Further development of macrophage foam cell formation is promoted by escalating inflammation of macrophages and other immunocytes. Overall, macrophage-related cholesterol metabolism and inflammation are two major factors related to the development of AS. Some food compounds could attenuate AS by increasing cholesterol efflux and inhibiting inflammation via targeting miRNAs. AS, atherosclerosis; ox-LDL, oxidized low-density lipoprotein

Fig. 2

Dietary compounds regulate AS-related macrophage cholesterol metabolism and inflammation via miRNAs. Different food compounds play atheroprotective roles by various miRNAs via different signaling pathways. (1) Diosgenin, EGCG, betulinic acid, CoQ10, and PCA could increase cholesterol efflux by inhibiting miR-19b, miR-33, miR-378, miR-33, and miR-10b, respectively. (2) Quercetin, AITC, apigenin, curcumin, and resveratrol could inhibit inflammatory response, through targeting to miR-155. CoQ10 could regulate inflammation via inhibiting miR-146a. With regard to the macrophage inflammation, different color lines represent the different dietary compounds regulate diverse signaling pathways via different miRNAs. AITC, allyl-isothiocyanate; CoQ10, coenzyme Q10; EGCG, epigallocatechin-3-gallate; PCA protocatechuic acid