An update on lipid oxidation and inflammation in cardiovascular diseases

Abstract

Cardiovascular diseases (CVD), including ischemic heart diseases and cerebrovascular diseases, are the leading causes of morbidity and mortality worldwide. Atherosclerosis is the major underlying factor for most CVD. It is well-established that oxidative stress and inflammation are two major mechanisms leading to atherosclerosis. Under oxidative stress, polyunsaturated fatty acids (PUFA)-containing phospholipids and cholesterol esters in cellular membrane and lipoproteins can be readily oxidized through a free radical-induced lipid peroxidation (LPO) process to form a complex mixture of oxidation products. Overwhelming evidence demonstrates that these oxidized lipids are actively involved in the inflammatory responses in atherosclerosis by interacting with immune cells (such as macrophages) and endothelial cells. In addition to lipid lowering in the prevention and treatment of atherosclerotic CVD, targeting chronic inflammation has been entering the medical realm. Clinical trials are under way to lower the lipoprotein (a) (Lp(a)) and its associated oxidized phospholipids, which will provide clinical evidence that targeting inflammation caused by oxidized lipids is a viable approach for CVD. In this review, we aim to give an update on our understanding of the free radical oxidation of LPO, analytical technique to analyze the oxidation products, especially the oxidized phospholipids and cholesterol esters in low density lipoproteins (LDL), and focusing on the experimental and clinical evidence on the role of lipid oxidation in the inflammatory responses associated with CVD, including myocardial infarction and calcific aortic valve stenosis. The challenges and future directions in understanding the role of LPO in CVD will also be discussed.