Apolipoprotein B Immunochemical Heterogeneity in Dialysed Patients with Chronic Renal Failure and Patients with Coronary Artery Stenosis

Electronegative LDL (LDL(؊)) is a minor subfraction of modified LDL present in plasma. Among its atherogenic characteristics, low affinity to the LDL receptor and high binding to arterial proteoglycans (PGs) could be related to abnormalities in the conformation of its main protein, apolipoprotein B-100 (apoB-100). In the current study, we have performed an immunochemical analysis using monoclonal antibody (mAb) probes to analyze the conformation of apoB-100 in LDL(؊). The study, performed with 28 anti-apoB-100 mAbs, showed that major differences of apoB-100 immunoreactivity between native LDL and LDL(؊) concentrate in both terminal extremes. The mAbs Bsol 10, Bsol 14 (which recognize the amino-terminal region), Bsol 2, and Bsol 7 (carboxyl-terminal region) showed increased immunoreactivity in LDL(؊), suggesting that both terminal extremes are more accessible in LDL(؊) than in native LDL. The analysis of in vitro-modified LDLs, including LDL lipolyzed with sphingomyelinase (SMase-LDL) or phospholipase A 2 (PLA 2 -LDL) and oxidized LDL (oxLDL), suggested that increased amino-terminal immunoreactivity was related to altered conformation due to aggregation. This was confirmed when the aggregated subfractions of LDL(؊) (agLDL(؊)) and oxLDL (ag-oxLDL) were isolated and analyzed. Thus, Bsol 10 and Bsol 14 immunoreactivity was high in SMase-LDL, ag-oxLDL, and agLDL(؊). The altered amino-terminal apoB-100 conformation was involved in the increased PG binding affinity of agLDL(؊) because Bsol 10 and Bsol 14 blocked its high PG-binding. These observations suggest that an abnormal conformation of the amino-terminal region of apoB-100 is responsible for the increased PG binding affinity of agLDL(؊).

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Relation of arteriographically defined coronary artery disease to serum lipoprotein particles mapped with monoclonal antibodies.

Fiévet

Nuttens

Ducimetière

et al. 1991

Circulation

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Background. This study was designed to investigate the relation of a molecular analysis of apolipoprotein B (apoB)-containing atherogenic lipoprotein particles to coronary artery disease (CAD) in middle-aged men.Methods and Results. Two groups of men were studied. The first consisted of 97 patients with angiographically documented CAD (greater than 50% stenosis of at least one coronary artery). The second group consisted of 145 subjects without symptomatic CAD, who served as controls. In both groups, measurements were obtained for total cholesterol level, triglyceride level, cholesterol contents in apoB-and nonapoB-containing particles (LpB, LpnonB), total apoB and apolipoprotein AI (apoAl levels), lipoprotein particles recognized by monoclonal antibodies anti-apoB (LpBL3, LpBL5, LpBL7) and anti-apoAl (LpAI-2G11). Taking into account age, body mass index, hypertension, diabetes, smoking habits, and drug consumption, the analysis showed that the mean levels of cholesterol were identical in both groups but differed when cholesterol content in LpB and LpnonB subfractions were assessed, thus reflecting an increase

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Apolipoprotein B Immunochemical Heterogeneity in Dialysed Patients with Chronic Renal Failure and Patients with Coronary Artery Stenosis

Cited by 4 publications

References 6 publications

Atherogenesis in Chronic Renal Failure

Atherogenesis in Chronic Renal Failure

Immunochemical Analysis of the Electronegative LDL Subfraction Shows That Abnormal N-terminal Apolipoprotein B Conformation Is Involved in Increased Binding to Proteoglycans

Relation of arteriographically defined coronary artery disease to serum lipoprotein particles mapped with monoclonal antibodies.

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