Oxidized phospholipids and lipoprotein(a): An update

Abstract

Over the past few years, there has been an undiminished interest in lipoprotein(a) [Lp(a)] and oxidized phospholipids (OxPLs), mainly carried on this lipoprotein. Elevated Lp(a) has been established as an independent causal risk factor for cardiovascular disease. OxPLs play an important role in atherosclerosis. The main questions that remain to be answered, however, is to what extent OxPLs contribute to the atherogenicity of Lp(a), what effect hypolipidaemic medications may have on their levels and the potential clinical benefit of their reduction. This narrative review aimed to summarize currently available data on OxPLs and cardiovascular risk, as well as the effect of established and emerging hypolipidaemic medications on Lp(a)‐OxPLs.

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

“…57 The new, under development, Lp(a)-lowering therapies potently reduce OxPL-apoB in parallel the reduction of plasma Lp(a) levels. 54 In addition to their role in cardiovascular disease, Lp(a) and OxPL-apoB may play an important role in the pathophysiology of calcific aortic valve stenosis (CAVS). 33,58 Moreover, it is known that plasminogen binds OxPLs covalently.…”

“…Some OxPLs exert anti‐inflammatory effects by negatively influencing TLR activation in response to microbial ligands in vitro and in vivo and interfering with pro‐inflammatory NF‐kB signaling. These inhibitory effects of OxPLs on TLRs activation are not restricted to a single TLR 54,55 . The transcription factor nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2), a well‐recognized target of OxPAPC, regulates the anti‐inflammatory effects of OxPLs 53 .…”

“…Importantly, the OxPLs carried by Lp(a) (OxPLs‐apoB) are associated with an increased incidence of coronary heart disease (CHD) 57 . The new, under development, Lp(a)‐lowering therapies potently reduce OxPL‐apoB in parallel the reduction of plasma Lp(a) levels 54 . In addition to their role in cardiovascular disease, Lp(a) and OxPL‐apoB may play an important role in the pathophysiology of calcific aortic valve stenosis (CAVS) 33,58 …”

“…Among the oxidized phospholipids, 1‐palmitoyl‐2‐azelaoyl‐ sn ‐glycero‐3‐phosphocholine (PAzPC), was the optimal substrate for Lp‐PLA 2 , followed by 1‐palmitoyl‐2‐succinoyl‐ sn ‐glycero‐3‐phosphocholine, 1‐palmitoyl‐2‐(5′‐oxo‐valeroyl)‐ sn ‐glycero‐3‐phosphocholine (POVPC), and 1‐palmitoyl‐2‐(9′‐oxo‐nonanoyl)‐ sn ‐glycero‐3‐phosphocholine (PONPC). A wide range of OxPLs molecules with biological activities that play a key role in atherosclerosis have been identified in plasma as well as in OxLDL particles 21,54,95–97 …”

“…These inhibitory effects of OxPLs on TLRs activation are not restricted to a single TLR. 54,55 The transcription factor nuclear factor (erythroid-derived 2)like 2 (Nrf2), a well-recognized target of OxPAPC, regulates the anti-inflammatory effects of OxPLs. 53 Most OxPLs could eliminate excessive inflammation, protect against oxidative stress and microbial infection, and mediate several homeostatic functions.…”