Pro-apoptotic low-density lipoprotein subfractions in type II diabetes.
OBJECTIVE
To test the hypothesis that differences in subfractions of circulating lipoproteins between diabetic and non-diabetic subjects exist and might contribute to the increased risk for atherosclerosis in type II diabetics.


RESULTS
LDL isolated from diabetic (D) and control subjects (N) were separated by FPLC into five subfractions (L1-L5). The fractional distributions of N- and D-LDL were not different, but the most strongly retained subfractions of D-LDL (D-L5) were markedly more pro-apoptotic to bovine aortic endothelial cells in vitro than were the other subfractions in D- or N-LDL. D-L5 induced time- and concentration-dependent apoptosis that was inhibited by z-VAD-fmk. The most electronegative D-LDL subfractions contained substantial amounts of apoproteins AI, E and CIII, higher concentrations of non-esterified fatty acids and LpPLA2, and lower trinitrobenzenesulfonic acid (TNBSA) reactivities. Electronegative subfractions of D-LDL exhibited longer lag times and lower net increases in absorbance at 234 nm with Cu-catalyzed oxidation in vitro.


CONCLUSIONS
The toxicities of electronegative subfractions of LDL from diabetic subjects to endothelial cells in vitro may be pivotal to vascular complications of diabetes in vivo, but the specific molecular alterations responsible for the toxicities of these subfractions of diabetic LDL are not known.
Yang
Chao-yuh
CY
Department of Medicine, Baylor College of Medicine, 6565 Fannin, MS A.601, Houston, TX 77030, USA. cyang@bcm.tmc.edu
Chen
Hsin-Hung
HH
Huang
Max T
MT
Raya
Joe L
JL
Yang
Jun-Hai
JH
Chen
Chu-Huang
CH
Gaubatz
John W
JW
Pownall
Henry J
HJ
Taylor
Addison A
AA
Ballantyne
Christie M
CM
Jenniskens
Floor A
FA
Smith
Charles V
CV
D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D002417:Cattle; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000145:classification; D008875:Middle Aged; D012307:Risk Factors
D008077:Lipoproteins, LDL