Mechanisms of Atherosclerosis Induced by Postprandial Lipemia

Abstract

Postprandial lipemia plays an important role in the formation, occurrence, and development of atherosclerosis, and it is closely related to coronary heart disease and other diseases involving endothelial dysfunction, oxidative stress, inflammation, and other mechanisms. Therefore, it has become a focus area for further research. The studies on postprandial lipemia mainly include TG, TRL, VLDL, CM, and remnant cholesterol. Diurnal triglyceride patterns and postprandial hyperlipidemia are very relevant and are now insufficiently covered. The possible mechanisms between postprandial lipemia and cardiovascular disease have been reviewed in this article by referring to relevant literature in recent years. The research progress on the effects of postprandial lipemia on endothelial function, oxidative stress, and inflammation is highlighted. The intervention of postprandial lipemia is discussed. Non-medicinal intervention such as diet and exercise improves postprandial lipemia. As medicinal intervention, statin, fibrate, ezetimibe, omega-3 fatty acids, and niacin have been found to improve postprandial lipid levels. Novel medications such as pemafibrate, PCSK9, and apoCIII inhibitors have been the focus of research in recent years. Gut microbiota is closely related to lipid metabolism, and some studies have indicated that intestinal microorganisms may affect lipid metabolism as environmental factors. Whether intervention of gut microbiota can reduce postprandial lipemia, and therefore against AS, may be worthy of further study.

Keywords: atherosclerosis; endothelial dysfunction; inflammation; oxidative stress; postprandial lipemia; triglyceride.

Figure 1

Mechanisms of atherosclerosis induced by postprandial lipemia. (1) Endothelial function: TG increased after HFM, while serum nitrite/nitrate levels and FMD decreased, suggesting endothelium dysfunction. (2) Oxidative stress: In terms of oxidative stress, TBARS, leukocyte ${\text{O}}_2^{-}$, and 8-PGF2 increased, and SOD, GSH-PX, and GSH decreased after HFM. ROS are produced in large quantities due to the increased levels of free fatty acids mediated by mitochondrial dissociation and β-oxidation. (3) Inflammation: ApoB100-containing lipoproteins enter into the arterial subendothelium, thus generating proinflammatory lipids, promoting the expression of adhesion factors such as, VCAM-1 and ICAM-1, which induce the augmentation of adhesion interaction with monocytes in turn, generating proinflammatory phenotypes and AS; TRL isolated from human plasma after HFM regulated TNF-α-induced VCAM-1 expression by regulating IRF-1-dependent transcription mechanism. The expression of CD11c on monocytes increased after a meal, and the purified monocytes internalized TRL isolated from postprandial blood through LDL receptor associated protein-1, which also caused the upregulation of CD11c. (4) Apoptosis: With the relation of cell cycle regulation and apoptosis, a group of genes of HUVEC differentially expressed in serum of postprandial hyperlipidemia after a meal, causing proliferation of HUVEC, significantly decreased and may be achieved by activating p53 network; the activities of pro-MMP-9, MPO, and caspase-3 increased significantly after a meal, showing apoptosis effect. (5) ER stress: The expansion of ER was significantly increased by HAEC treated with postprandial TRL, and the production of TRL increased the adhesion of VCAM-1-dependent monocytes to inflammatory endothelium, indicating ER stress plays a role in the regulation of VCAM-1 transcription in endothelial cells during the process of AS. (6) Mitochondrial dynamics: The binding rate of GDP increased by 85% after HFM, and the increase was the largest in early postprandial period. TG, triglyceride; HFM, high-fat meal; FMD, flow-mediated vasodilation; TBARS, thiobarbiturate reactants; 8-PGF2, 8-external prostaglandin F2; SOD, superoxide dismutase; GSH-PX, glutathione peroxidase; ROS, reactive oxygen species; VCAM-1, vascular cell adhesion molecule-1; ICAM-1, intercellular adhesion molecule-1; AS, atherosclerosis; TRL, TG-rich lipoprotein; LDL, low-density lipoprotein; HUVEC, human umbilical vein endothelial cell; ER, endoplasmic reticulum; HAEC, human aortic endothelial cell.