Modulation of angiogenic processes in cultured endothelial cells by low density lipoproteins subfractions from patients with familial hypercholesterolemia

Ming Hong Tai, Shiao Mei Kuo, Hui Ting Liang, Kuan Rau Chiou, Hing Chung Lam, Ching Mei Hsu, Henry J. Pownall, Hsin Hung Chen, Max T. Huang, Chao Yuh Yang

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30 Citations (Scopus)

Abstract

Objective: Electronegative low density lipoprotein (LDL) subfractions are cytotoxic to endothelial cells. To continue our study of homozygotic familial hypercholesterolemic (FH)-LDL, we report the effects of FH-LDL subfractions (FH-L1 to FH-L5) on the angiogenic processes in cultured endothelial cells. Methods and results: Subconfluent bovine aortic endothelial cells (BAEC) were treated with LDL subfractions (20 μg/ml), and the effects on angiogenic functions, including cell proliferation, migration, apoptosis, tube formation, secretion of matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF) were determined. The electronegative FH-L4 and FH-L5 inhibited cell proliferation while the other FH-LDL subfractions and LDL from normocholesterolemic subjects (N-LDL) had negligible effects. Like Cu2+ ox-LDL, FH-L5 strongly inhibited endothelial cell viability and FH-L4 had a milder effects. Similarly, FH-L4 and FH-L5 but not the other subfractions retarded cell migration, induced cell apoptosis, and perturbed tube formation by BAEC in matrigel. FH-L5 inhibited secretion of MMP-2 and MMP-9 by BAEC without affecting their endogenous levels. In contrast, FH-L5 increased the VEGF expression in endothelial cells. Conclusions: Our results show for the first time that FH-L5, a circulating LDL subfraction from hypercholesterolemic patients, modulates various angiogenic processes, thereby dysregulating endothelial function in a way that may be atherogenic.

Original languageEnglish
Pages (from-to)448-457
Number of pages10
JournalAtherosclerosis
Volume186
Issue number2
DOIs
Publication statusPublished - Jun 1 2006
Externally publishedYes

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Keywords

  • Angiogenesis
  • Apoptosis
  • Electronegative LDL
  • Endothelial cell
  • Matrix metalloproteinase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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