In:
Diabetes, American Diabetes Association, Vol. 52, No. 5 ( 2003-05-01), p. 1240-1247
Abstract:
This study compares the effects of LDL glycated either in vitro (LDLiv) or in vivo in diabetic patients (LDLD) on apoptosis, proliferation, and associated protein expression in cultured human umbilical vein endothelial cells. At 100 mg/l, both LDL species considerably increase apoptosis (LDLiv 63%, LDLD 40%; P & lt; 0.05) compared with intraindividual nonglycated LDL subfractions. Considering its lower degree of glycation (LDLD 5–10%, LDLiv 42%), LDLD’s relative proapoptotic activity is 2.7-fold greater than that of LDLiv. Glycated LDL-induced apoptosis is associated with increased expression of apoptosis promotors (LDLiv: bak 88%, CPP-32 49%; LDLD: bak 18%, CPP-32 11%; P & lt; 0.05) and is attenuated by caspase inhibitors. Glycated LDL’s antiproliferative activity (LDLiv −34%, LDLD −9%; P & lt; 0.01) relates to reduction (P & lt; 0.05) of cyclin D3 (LDLiv −27%, LDLD −24%) and of hypo- (LDLiv −22%, LDLD −19%) and hyperphosphorylated (LDLiv −53%, LDLD −22%) retinoblastoma protein and is paralleled by reduced expression of endothelial nitric oxide synthase (LDLiv −30%, LDLD −23%). In response to lipoprotein lipase, LDLD more markedly triggers endothelial apoptosis (27.1-fold) compared with LDLiv, suggesting that LDLD owns a higher potential for endothelial cell damage than LDLiv. The observed behavior of LDLD versus LDLiv could be of clinical importance and well relate to differences in structure and cellular uptake of LDLD compared with LDLiv.
Type of Medium:
Online Resource
ISSN:
0012-1797
,
1939-327X
DOI:
10.2337/diabetes.52.5.1240
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2003
detail.hit.zdb_id:
1501252-9
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