Oxidized phospholipids and lipoprotein‐associated phospholipase A₂ (Lp‐PLA₂) in atherosclerotic cardiovascular disease: An update

Abstract

Inflammation and oxidative stress conditions lead to a variety of oxidative modifications of lipoprotein phospholipids implicated in the occurrence and development of atherosclerotic lesions. Lipoprotein-associated phospholipase A2 (Lp-PLA 2 ) is established as an independent risk biomarker of atherosclerosis-related cardiovascular disease (ASCVD) and mediates vascular inflammation through the regulation of lipid metabolism in the blood and in atherosclerotic lesions. Lp-PLA 2 is associated with low-and high-density lipoproteins and Lipoprotein (a) in human plasma and specifically hydrolyzes oxidized phospholipids involved in oxidative stress modification. Several oxidized phospholipids (OxPLs) subspecies can be detoxified through enzymatic degradation by Lp-PLA 2 activation, forming lysophospholipids and oxidized nonesterified fatty acids (OxNEFAs). Lysophospholipids promote the expression of adhesion molecules, stimulate cytokines production (TNF-α, IL-6), and attract macrophages to the arterial intima. The present review article discusses new data on the functional roles of OxPLs and Lp-PLA 2 associated with lipoproteins.

Metformin Monotherapy Alters the Human Plasma Lipidome Independent of Clinical Markers of Glycemic Control and Cardiovascular Disease Risk in a Type 2 Diabetes Clinical Cohort

“…Oxidized phospholipids have previously been shown to increase in insulin resistant individuals and be associated with the pathogenesis of oxidative stress-related diseases, including CVD (Fruhwirth et al, 2007;Sun et al, 2016;Que et al, 2018). Yet, in previous work, increased circulating oxidized phospholipids correlated with Lp-PLA2 levels (Pantazi et al, 2022). In our study, we found oxidized phospholipids were specifically elevated in the T2D-DL group, even though there was no statistically significant difference between the number of subjects in the T2D-DL and T2D-M groups who had clinically elevated Lp-PLA2 levels.…”

The Relation between Deregulated Immune Milieu and Atherogenic Lipids Might Underlie the Development of Pregnancy-induced Hypertensive Disorders

“…A recent study suggested a mechanism for this relation depends on the generation of ROS causing oxidized phospholipids subspecies that were degraded enzymatically by activation of lipoprotein-associated phospholipase A2 forming lysophospholipids which in turn stimulate the production of the inflammatory cytokines; TNF-α and IL-6, promote the expression of adhesion molecules and attract macrophages to the arterial intima causing atherosclerotic changes [37] .…”

Deciphering Complex Interactions in Bioactive Lipid Signaling

“…From the metabolic pathways of EICs, ECBs and SPMs shown in Figure 1 , Figure 2 and Figure 3 , it is apparent that these families of bioactive lipids share key enzymes, such as the lipase responsible for the release from phospholipid precursors (PLA 2 ) and three oxygenases able to generate from AA: (i) epoxyeicosatrienoic acids (CYP450); (ii) 12-hydroxyeicosatetraenoic acids (12-LOX); and (iii) cyclic prostanoid(-like) oxidative derivatives (COX-2). Of note, PLA 2 belongs to a superfamily of enzymes that play major roles in several pathophysiological processes, e.g., mast cell biology [ 45 ], atherosclerotic cardiovascular disease [ 46 ], and gastrointestinal diseases [ 47 ]. Unsurprisingly, PLA 2 enzymes are able to mobilize unique bioactive lipids in multiple ways that are spatiotemporally regulated, thus triggering distinct signaling pathways.…”