Electronegative low-density lipoprotein: Origin and impact on health and disease

Abstract

Oxidative modifications in lipoproteins (LP), especially in low-density lipoproteins (LDL), are associated with initiation and progression of atherosclerosis. The levels of a sub-fraction of LDL with oxidative characteristics, named electronegative LDL [LDL(-)], minimally oxidized LDL, and minus LDL, are known to be increased in subjects with familial hypercholesterolemia, hypertriglyceridemia, nonalcoholic steatohepatitis, diabetes mellitus, coronary artery disease, patients undergoing hemodialysis, and athletes after aerobic exercise. In addition to the oxidative profile, physical and biological characteristics of LDL(-) consist of nonenzymatic glycosylation, increased expression and activity of platelet-activating factor acetylhydrolase (PAF-AH) and phospholipase A(2) (PLA(2)), enriched NEFA content, hemoglobin and ApoB-100 cross-linking, and increase in ApoC-III and ApoE in LDL. Herein, we summarize the state of the art of the up-to-date body of knowledge on the possible origin and impact of LDL(-) in health and disease. Further, the potential perspectives of using LDL(-) as a biomarker in conditions under metabolic stress are also discussed.

Reassessing lipid metabolism and its potentialities in the prediction of cardiovascular risk

“…This stimulation may be detected by the increased number of mononuclear cells, as well as other markers, such as antibodies targeting modified lipoproteins, MCP-1, interleukins, IFN-γ, TNF-α, and platelet-derived growth factor (25).…”

“…Another target of this investigation has been the electronegative LDL (LDL(-) or minimally modified LDL), produced by oxidation and other processes, such as non-enzymatic glycosylation, hyperactivity of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), enrichment by non-esterified fatty acids, cross-binding with hemoglobin and apo B-100, and increase in apo C-III and apo E content (17,25). Modified LDL particles have lower affinity by B/E receptors, which affects liver catabolism, increases the content of cholesteryl esters in macrophages, and alters endothelial function (26).…”

Lipoproteins and Cancer

“…While LDL-C may contribute to cancer risk or prognosis, as in cardiovascular disease oxLDL may also play a role. OxLDL is present as a small percentage of total LDL in normal individuals, but the percentage of oxLDL may increase in pathological states (Holvoet, Lee et al 2008;Mello, da Silva et al 2011). An oxLDL receptor (OLR1) and was recently identified experimentally as part of gene signature responsible for transformation, tumor growth, and proliferation in multiple cancer cell lines (Hirsch, Iliopoulos et al 2010).…”

Reactivity of Direct Assays for Low-Density Lipoprotein (LDL) Cholesterol Toward Charge-Modified LDL in Hypercholesterolemia

“…12, 13 Hypertriglyceridemia is associated with both increased sdLDL 14 and electronegative LDL, 11 which are atherogenic. 11,15, 16 The reactivity of homogeneous assays for LDL-C toward atherogenic modified LDL has not been examined, which may, however, be clinically important.…”