Electronegative low density lipoprotein subform (LDL - ) is increased in type 2 (non-insulin-dependent) microalbuminuric diabetic patients and is closely associated with LDL susceptibility to oxidation

Moro, E; Zambon, Carlo-Federico; Pianetti, S.; Cazzolato, G.; Pais, M; Bon, Gabriele Bittolo

doi:10.1007/s005920050123

Cited by 40 publications

(24 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In accordance with this, we recently demonstrated that free (unesterified) 7-ketocholesterol levels are significantly higher in the LDL of patients with well-controlled type 2 diabetes than in the LDL of healthy subjects [53]. Furthermore, it has been shown that the percentage of electronegative LDL in plasma is higher in microalbuminuric diabetic patients than in normoalbuminuric diabetic patients or control subjects [67]. Plasma levels of oxidised LDL, as measured by sandwich ELISA, were increased in individuals with IGT compared with control subjects after adjusting for age and BMI [68], and are higher in type 2 diabetic patients with macroalbuminuria than in patients with normo-or microalbuminuria or healthy control subjects [69].…”

Section: Measurement Of Ldl Oxidationsupporting

confidence: 58%

Clinical significance of the physicochemical properties of LDL in type 2 diabetes

2005

View full text Add to dashboard Cite

Atherosclerosis is the leading cause of death in type 2 diabetes. LDL cholesterol and atherosclerosis are related, both in healthy people and those with diabetes; however, people with diabetes are more prone to atheroma, even though their LDL cholesterol levels are similar to those in their non-diabetic peers. This is because LDL particles are modified in the presence of diabetes to become more atherogenic. These modifications include glycation in response to high plasma glucose levels; oxidative reactions mediated by increased oxidative stress; and transfer of cholesterol ester, which makes the particles smaller and denser. The latter modification is strongly associated with hypertriglyceridaemia. Oxidatively and non-oxidatively modified LDL is involved in plaque formation, and may thus contribute to the accelerated atherosclerosis. This review discusses the techniques currently used to determine the physicochemical properties of LDL, and examines the evidence that modification of these properties plays a role in the accelerated atherosclerosis associated with type 2 diabetes.

show abstract

Section: Measurement Of Ldl Oxidationsupporting

confidence: 58%

Clinical significance of the physicochemical properties of LDL in type 2 diabetes

2005

View full text Add to dashboard Cite

show abstract

“…11,12 High concentrations of LDL(Ϫ) have been associated with major risk factors for cardiovascular disease, including hypercholesterolemia 13 and type 2 diabetes mellitus. 14 Apparently more toxic still is L5, which is the most electronegative of the LDL subfractions separable by highcapacity ion-exchange chromatography according to charge that we first described in 2003. 11,15 L5 is present in hypercholesterolemic subjects and those with type 2 diabetes but not in healthy subjects with clinically normal lipid concentrations.…”

mentioning

confidence: 99%

Mediation of Electronegative Low-Density Lipoprotein Signaling by LOX-1

Yang

Burns

et al. 2009

Circulation Research

129

131

View full text Add to dashboard Cite

Abstract-The lectin-like oxidized LDL receptor LOX-1 mediates endothelial cell (EC) uptake of experimentally prepared copper-oxidized LDL (oxLDL). To confirm the atherogenic role of this receptor cloned against copper-oxLDL, we examined whether it mediates EC uptake of L5, an electronegative LDL abundant in dyslipidemic but not normolipidemic human plasma. Hypercholesterolemic (LDL-cholesterol, Ͼ160 mg/dL) human LDL was fractionated into L1-L5, increasingly electronegative, by ion-exchange chromatography. In cultured bovine aortic ECs (BAECs), L5 upregulated LOX-1 and induced apoptosis. Transfection of BAECs with LOX-1-specific small interfering RNAs (siLOX-1) minimized baseline LOX-1 production and restrained L5-induced LOX-1 upregulation. Internalization of labeled L1-L5 was monitored in BAECs and human umbilical venous ECs by fluorescence microscopy. LOX-1 knockdown with siLOX-1 impeded the endocytosis of L5 but not L1-L4. In contrast, blocking LDL receptor with RAP (LDL receptor-associated protein) stopped the internalization of L1-L4 but not L5. Although chemically different, L5 and oxLDL competed for EC entry through LOX-1. Via LOX-1, L5 signaling hampered Akt phosphorylation and suppressed EC expression of fibroblast growth factor-2 and Bcl-2. L5 also selectively inhibited Bcl-xL expression and endothelial nitric oxide synthase phosphorylation but increased synthesis of Bax, Bad, and tumor necrosis factor-␣.

show abstract

“…Plasma LDL(2) is increased in subjects at high risk for cardiovascular disease as a result of hypercholesterolemia (10)(11)(12), hypertriglyceridemia (11,13), diabetes (14)(15)(16)(17), or coronary artery disease (18). Simvastatin therapy reduces the proportion of LDL(2) without modifying its oxidizability (12).…”

mentioning

confidence: 99%

Dynamics of dense electronegative low density lipoproteins and their preferential association with lipoprotein phospholipase A2

Gaubatz

Gillard

Massey

et al. 2007

Journal of Lipid Research

View full text Add to dashboard Cite

Small, dense, electronegative low density lipoprotein [LDL(2)] is increased in patients with familial hypercholesterolemia and diabetes, populations at increased risk for coronary artery disease. It is present to a lesser extent in normolipidemic subjects. The mechanistic link between small, dense LDL(2) and atherogenesis is not known. To begin to address this, we studied the composition and dynamics of small, dense LDL(2) from normolipidemic subjects. NEFA levels, which correlate with triglyceride content, are quantitatively linked to LDL electronegativity. Oxidized LDL is not specific to small, dense LDL(2) or lipoprotein [a] (i.e., abnormal lipoprotein). Apolipoprotein C-III is excluded from the most abundant LDL (i.e., that of intermediate density: 1.034 , d , 1.050 g/ml) but associated with both small and large LDL(2). In contrast, lipoproteinassociated phospholipase A 2 (LpPLA 2 ) is highly enriched only in small, dense LDL(2). The association of LpPLA 2 with LDL may occur through amphipathic helical domains that are displaced from the LDL surface by contraction of the neutral lipid core.-Gaubatz, J. W., B. K. Gillard, J. B. Massey, R. C. Hoogeveen, M. Huang, E. E. Lloyd, J. L. Raya, C-y. Yang, and H. J. Pownall. Dynamics of dense electronegative low density lipoproteins and their preferential association with lipoprotein phospholipase A 2 . J. Lipid Res. 2007. 48: 348-357. Supplementary key words atherogenesis & fatty acid & apo B-100Although low density lipoprotein-cholesterol is a risk factor for cardiovascular disease, an expanding body of evidence suggests that one or more minor LDL subfractions serve as the atherogenic agent. One hypothesis is that LDL enters the arterial wall, where its lipids are oxidatively modified, thereby initiating a series of biochemical processes that culminate in lesion formation (1). Nonetheless, modified LDL present in the circulation also has atherogenic properties (2), as indicated by the correlation of atherosclerosis with levels of oxidized plasma LDL (3-5). Plasma contains several forms of modified LDL, including heterogeneously oxidized LDL (6), glycated LDL from diabetic subjects (7), and desialylated LDL (8). Importantly, plasma from both normal and dyslipidemic patients contains electronegative low density lipoprotein [LDL(2)] (9); however, there have been few comprehensive studies of LDL(2) in normolipidemic subjects.Plasma LDL(2) is increased in subjects at high risk for cardiovascular disease as a result of hypercholesterolemia (10-12), hypertriglyceridemia (11, 13), diabetes (14-17), or coronary artery disease (18). Simvastatin therapy reduces the proportion of LDL(2) without modifying its oxidizability (12). Relative to normal LDL, LDL(2) has 1) lower vitamin E content; 2) increased lipid peroxidation, as assessed by thiobarbituric acid-reactive substances and conjugated dienes; 3) more highly aggregated apolipoprotein B (apoB); 4) reduced affinity for the LDL receptor; 5) greater density and is more readily oxidized; and 6) higher lipoperoxide c...

show abstract

Electronegative low density lipoprotein subform (LDL - ) is increased in type 2 (non-insulin-dependent) microalbuminuric diabetic patients and is closely associated with LDL susceptibility to oxidation

Cited by 40 publications

References 0 publications

Clinical significance of the physicochemical properties of LDL in type 2 diabetes

Clinical significance of the physicochemical properties of LDL in type 2 diabetes

Mediation of Electronegative Low-Density Lipoprotein Signaling by LOX-1

Dynamics of dense electronegative low density lipoproteins and their preferential association with lipoprotein phospholipase A2

Contact Info

Product

Resources

About