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.

A Boost in Mitochondrial Activity Underpins the Cholesterol-Lowering Effect of Annurca Apple Polyphenols on Hepatic Cells

“…Our previously published studies have already shown that AAE reduces total cholesterol levels both in vitro, in hepatic cultured cells, as well as in vivo, in humans affected by mild hypercholesterolemia [29,42]. Our results confirm those published by other groups and presenting similar effects exerted by other polyphenolic extracts [16,17,43,44,45,46,47]. However, whether the cholesterol lowering effect of AAE is due to i) reduced cholesterogenesis, ii) increased cholesterol excretion or iii) increased conversion of cholesterol into bile acids remains elusive.…”

Mechanism overview and target mining of atherosclerosis: Endothelial cell injury in atherosclerosis is regulated by glycolysis (Review)

“…Ox-LDL exhibits strong affinity for scavenger receptors found on mononuclear macrophages, leading to its quick internalisation ( 21 ). However, Ox-LDL is toxic for macrophages, causing them to become activated, rapidly proliferate, aggregate and degenerate ( 22 ). Finally, the macrophages undergo apoptosis and become foam cells, which then aggregate to form AS lipid plaques.…”

The Anti-Inflammatory Properties of Phytochemicals and Their Effects on Epigenetic Mechanisms Involved in TLR4/NF-κB-Mediated Inflammation

“…In addition, many plant-derived compounds were recently suggested to exert their anti-inflammatory effect through regulating the expression of proinflammatory miRNAs, especially those upregulated after NF-kB activation (120). Although a few reports indicate the precise mechanisms that regulate or deregulate the expression of miRNAs, growing evidence suggests that phytochemicals regulate the expression of miRNAs by interfering with the processes associated with the miRNAs processing and maturation, and these phytochemicalmediated alterations in miRNAs biosynthesis machinery could in part contribute to the miRNAs dysregulation by either increasing or decreasing their levels (121,122).…”