The Oxidized Lipoproteins In Vivo: Its Diversity and Behavior in the Human Circulation

Abstract

A high concentration of low-density lipoproteins (LDLs) in circulation has been well-known as a major risk factor for cardiovascular diseases. The presence of oxidized LDLs (oxLDLs) in atherosclerotic lesions and circulation was demonstrated using anti-oxLDL monoclonal antibodies. The so-called “oxLDL hypothesis”, as a mechanism for atherosclerosis development, has been attracting attention for decades. However, the oxLDL has been considered a hypothetical particle since the oxLDL present in vivo has not been fully characterized. Several chemically modified LDLs have been proposed to mimic oxLDLs. Some of the subfractions of LDL, especially Lp(a) and electronegative LDL, have been characterized as oxLDL candidates as oxidized phospholipids that stimulate vascular cells. Oxidized high-density lipoprotein (oxHDL) and oxLDL were discovered immunologically in vivo. Recently, an oxLDL-oxHDL complex was found in human plasma, suggesting the involvement of HDLs in the oxidative modification of lipoproteins in vivo. In this review, we summarize our understanding of oxidized lipoproteins and propose a novel standpoint to understand the oxidized lipoproteins present in vivo.

Hyperglycaemia Aggravates Oxidised Low-Density Lipoprotein-Induced Schwann Cell Death via Hyperactivation of Toll-like Receptor 4

“…We used CuSO 4 for oxLDL preparation, which is the most widely used method for oxLDL preparation in vitro. However, LDL oxidised with copper may not reproduce the complete features of oxLDL generated in vivo as described previously [ 37 ]. In addition, our findings are limited to a cellular model; further in vivo experiments are required to fully establish the significance of TLR4 signalling in the aetiology of diabetic neuropathy.…”

Trained Innate Immunity in Animal Models of Cardiovascular Diseases

“…Cellular uptake of LDL does not result in massive cholesterol accumulation, because intracellular cholesterol downregulates the LDL receptor (LDLr). However, oxidation of LDL in serum or the vascular wall by enzymatic or non-enzymatic mechanisms (lipoxygenases, myeloperoxidases, metal ions) results in the generation of oxidized LDL variants (oxLDL) that do not bind to the LDLr but are internalized by scavenger receptors [81,82]. Scavenger receptors, such as SR-A and CD36, are not downregulated by oxLDL, and mediate massive cholesterol uptake that results in the formation of foam cells [81].…”

“…However, oxidation of LDL in serum or the vascular wall by enzymatic or non-enzymatic mechanisms (lipoxygenases, myeloperoxidases, metal ions) results in the generation of oxidized LDL variants (oxLDL) that do not bind to the LDLr but are internalized by scavenger receptors [81,82]. Scavenger receptors, such as SR-A and CD36, are not downregulated by oxLDL, and mediate massive cholesterol uptake that results in the formation of foam cells [81]. Cell-culture studies with human monocytes revealed that oxidized LDL can also induce epigenetic modifications that generate innate memory and result in increased cytokine release after restimulation with toll-like receptor 2 (TLR2) or TLR4 agonists [35].…”

Lipoprotein Oxidation, Genetic Expression and Polymorphism of Apo A and B Gene in Patients with Coronary Artery Disease in A Pakistani Punjabi Population

“…The most prevalent cardiovascular disease is coronary artery disease (CAD). There is growing evidence that oxidative alteration of lipoproteins is crucial to the development and progression of atherosclerosis (Itabe & Obama 2023). Oxidized low density lipoprotein (oxLDL) has been implicated in CAD progression, promoting inflammation and atherosclerosis.…”