Pro-apoptotic low-density lipoprotein subfractions in type II diabetes

Chao yuh Yang, Hsin Hung Chen, Max T. Huang, Joe L. Raya, Jun Hai Yang, Chu Huang Chen, John W. Gaubatz, Henry J. Pownall, Addison A. Taylor, Christie M. Ballantyne, Floor A. Jenniskens, Charles V. Smith

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

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. Methods and 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.

Original languageEnglish (US)
Pages (from-to)283-291
Number of pages9
JournalAtherosclerosis
Volume193
Issue number2
DOIs
StatePublished - Aug 1 2007

Keywords

  • Apoptosis
  • Atherosclerosis
  • Diabetes
  • Electronegative LDL
  • Fatty acids
  • Lipoprotein phospholipase A2

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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