Electronegative low-density lipoprotein

Abstract

Recent findings suggest that LDL(-) could contribute to atherogenesis via several mechanisms, including proinflammatory, proapoptotic and anti-angiogenesis properties. Further studies are required to define the role of LDL(-) in atherogenesis more precisely and to clarify mechanisms involved in endothelial cell activation.

Proteomic approach to study the effects of various oxidatively modified low-density lipoprotein on regulation of protein expression in human umbilical vein endothelial cell

“…LDL derived from atherosclerotic plaques is probably the most physiologically relevant LDL, but is limited in availability. FH-L5, isolated from circulation without artificial modification, has proven to be atherogenic and is easier to obtain than a-LDL (Chen et al, 2000;Chen et al, 2003;Sanchez-Quesada et al, 2004). Recently, much research has focused on its biological functions Yang et al, 2003;Benitez et al, 2004;Tai et al, 2006).…”

Low-Density Lipoprotein Electronegativity Is a Novel Cardiometabolic Risk Factor

“…Avogaro and colleagues [8] were the first to report that LDL could be divided into electropositive [LDL (+)] and electronegative [LDL (–)] fractions by using ion-exchange chromatography. Since then, others have described the chemical and functional properties of these dichotomized LDL subfractions [9]–[12]. The proportion of plasma LDL(–) has been shown to be increased in patients with high cardiovascular risks [13] such as hyperlipidemia, diabetes, severe renal disease, and nonalcoholic steatohepatitis, as well as in patients with coronary syndromes when compared with healthy individuals.…”

“…In addition, L5 is not internalized by the normal LDL receptor but by the lectin-like oxidized LDL receptor- 1 (LOX-1), which in turn leads to endothelial cell apoptosis [20]. Circulating L5 has been shown to be pro-atherogenic [9] and is the only subfraction of human LDL that induces endothelial dysfunction and atherogenic responses in cultured vascular cells [14], [15], [21]. Although L5 has a role in promoting atherogenesis, it remains unknown whether L5 levels increase with the progression of CVD.…”

The inflammatory properties of electronegative low-density lipoprotein from type 1 diabetic patients are related to increased platelet-activating factor acetylhydrolase activity

“…Making use of this characteristic, an electronegative modified LDL subfraction (LDL[−]) can be isolated from human plasma by anion exchange chromatography [8]. LDL(−) exhibits a variety of atherogenic and inflammatory properties [9], including abnormal density distribution [10], impaired affinity for the LDL receptor [8,11], cytotoxicity [12,13], apoptosis [14] and induction of inflammatory molecules production in cultured endothelial cells, such as interleukin-8 (IL-8), monocyte chemotactic protein (MCP-1) [15,16] and TNF-α-induced vascular cell adhesion molecule (VCAM) [17]. Moreover, the proportion of LDL(−) is increased in diseases with high cardiovascular risk such as familial hypercholesterolaemia (FH) [11,18], hypertriglyceridaemia [10], renal failure disease [19] and type 1 and type 2 diabetes mellitus [20][21][22][23].…”

“…Our group previously reported that optimisation of glycaemic control with intensive insulin therapy decreases the proportion of LDL (−) in subjects with type 1 diabetes [20,21], which led us to hypothesise that non-enzymatic glycosylation could be involved in the generation of LDL(−) in these patients. Although extensive characterisation of LDL(−) from normolipaemic and FH subjects has been reported [8][9][10][11][12][13][14][15][16][17], no data exist on the physicochemical characteristics of LDL (−) from diabetic subjects. Thus, the aim of the current work was to ascertain whether non-enzymatic glycosylation of LDL could directly induce the formation of LDL(−), thereby causing an increased proportion of LDL(−) in type 1 diabetic patients, and to determine the physicochemical and biological characteristics of LDL(−) isolated from these patients.…”