Implication of lipoprotein associated phospholipase A2 activity in oxLDL uptake by macrophages

Abstract

Supplementary key words oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine • lysophosphatidylcholine • moderately oxidized LDL • heavily oxidized LDL Oxidation of LDL is considered as a prerequisite event in the atherogenic process. LDL oxidation is mediated by endothelial cells, smooth muscle cells, and macrophages in the arterial intima and oxidized LDL (oxLDL) are found in abundance into atherosclerotic lesions ( 1-6 ). Oxidative modifi cation of LDL includes i ) peroxidation of the lipids, ii ) conversion of PC to lysophosphatidylcholine ( lysoPC) (up to 50% depending on the extension of the oxidation), iii ) an increase in density, iv ) an increase in net negative charge resulting in increased electrophoretic mobility, v ) breakdown of apolipoprotein B (ApoB) into smaller peptides, and vi ) binding of oxidized lipids on ApoB ( 2,7,8 ). Oxidation of LDL has various atherogenic effects such as increased uptake by macrophages and smooth muscle cells leading to foam cell formation, increased production of adhesion molecules, induction of monocytes/macrophages and smooth muscle cell prolif-

Carotid intima media thickness is associated with plasma lipoprotein-associated phospholipase A2 mass in nondiabetic subjects but not in patients with type 2 diabetes

“…Indirect support of this possibility stems from the observation of a greater IMT in diabetic subjects with partial genetic PLA2G7 deficiency [29]. Second, Lp‐PLA 2 may become inactivated during LDL oxidation in vitro [30]. This would raise the possibility that the occurrence of inactivated Lp‐PLA 2 consequent to enhanced LDL oxidation could mask a relationship between circulating Lp‐PLA 2 levels and subclinical atherosclerosis.…”

OxLDL up-regulates Niemann–Pick type C1 expression through ERK1/2/COX-2/PPARα-signaling pathway in macrophages

“…Dysregulation of the balance of cholesterol influx and cholesterol efflux will lead to excessive accumulation of cholesterol in macrophages and their transformation into foam cells. Within the cells, modified LDL-derived cholesterol esters are hydrolyzed in lysosomes, and cholesterol is probably initially transported to the plasma membrane where it integrates the cell membrane [29]. Trafficking of cholesterol from the LE/ LY to the plasma membrane is a protein-mediated process principally controlled by NPC1 [30].…”

Higher lipoprotein-associated phospholipase A2 levels are associated with coronary atherosclerosis documented by coronary angiography

“…10,18,19 The progressive inactivation of Lp-PLA2 during LDL oxidation leads to increased oxLDL uptake by macrophages, which could be attributed primarily to the increased uptake of the oxidized phospholipid-enriched lipid moiety of oxLDL. 20 The oxidized phospholipids of oxLDL accumulate in atherosclerotic lesions and up-regulate Lp-PLA2 production. 21 Hence, oxLDL and Lp-PLA2 are closely associated in the process of coronary atherosclerosis.…”