S Braschi1, M Geoffrion, A Nguyen, Y Gaudreau, R W Milne. 1. Endocrinology Division, Medicine Department, University of Ottawa, Ottawa Hospital, Riverside Campus, 1967 Riverside Drive, Ottawa, ON, K1H 7W9, Canada. sbraschi@ottawaheart.ca
Abstract
AIMS/HYPOTHESIS: When LDLs are exposed to glucose in vitro, glycation of apolipoprotein B100 (apoB) leads to a loss in its affinity for the LDL receptor and reproducible alterations in the immunoreactivity of specific apoB epitopes, including several epitopes close to the LDL receptor binding site. The aim of this work was to determine if similar immunological changes are observed in vivo in LDLs of diabetic and end-stage renal disease (ESRD) patients. SUBJECTS, MATERIALS AND METHODS: The immunoreactivity of LDLs isolated from 14 diabetic patients with normal renal function and 13 patients with ESRD was studied with a panel of 25 well-characterised anti-apoB monoclonal antibodies. RESULTS: Although diabetic and ESRD LDLs showed evidence of glycation modification, none of the changes in the apoB immunoreactivity induced by glucose in vitro was observed in vivo, including those for epitopes close to the LDL receptor binding domain. CONCLUSIONS/ INTERPRETATION: These results suggest that in vivo glycation of LDLs is a complex process that is not mimicked by in vitro exposure of LDLs to high concentrations of glucose. This questions the clinical significance of the in vitro glycation studies used to understand the pathophysiological consequences of LDL glycation in diabetes and ESRD.
AIMS/HYPOTHESIS: When LDLs are exposed to glucose in vitro, glycation of apolipoprotein B100 (apoB) leads to a loss in its affinity for the LDL receptor and reproducible alterations in the immunoreactivity of specific apoB epitopes, including several epitopes close to the LDL receptor binding site. The aim of this work was to determine if similar immunological changes are observed in vivo in LDLs of diabetic and end-stage renal disease (ESRD) patients. SUBJECTS, MATERIALS AND METHODS: The immunoreactivity of LDLs isolated from 14 diabeticpatients with normal renal function and 13 patients with ESRD was studied with a panel of 25 well-characterised anti-apoB monoclonal antibodies. RESULTS: Although diabetic and ESRD LDLs showed evidence of glycation modification, none of the changes in the apoB immunoreactivity induced by glucose in vitro was observed in vivo, including those for epitopes close to the LDL receptor binding domain. CONCLUSIONS/ INTERPRETATION: These results suggest that in vivo glycation of LDLs is a complex process that is not mimicked by in vitro exposure of LDLs to high concentrations of glucose. This questions the clinical significance of the in vitro glycation studies used to understand the pathophysiological consequences of LDL glycation in diabetes and ESRD.
Authors: Sarama Saha; Juergen Graessler; Peter E H Schwarz; Claudia Goettsch; Stefan R Bornstein; Steffi Kopprasch Journal: Mol Cell Biochem Date: 2012-03-01 Impact factor: 3.396