title: Modulation of angiogenic processes in cultured endothelial cells by low density lipoproteins subfractions from patients with familial hypercholesterolemia.
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.
  
  
  RESULTS
  Subconfluent bovine aortic endothelial cells (BAEC) were treated with LDL subfractions (20 microg/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.
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Tai
authors.forename: Shiao-Mei
authors.initials: SM
authors.lastname: Kuo
authors.forename: Hui-Ting
authors.initials: HT
authors.lastname: Liang
authors.forename: Kuan-Rau
authors.initials: KR
authors.lastname: Chiou
authors.forename: Hing-Chung
authors.initials: HC
authors.lastname: Lam
authors.forename: Ching-Mei
authors.initials: CM
authors.lastname: Hsu
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Pownall
authors.forename: Hsin-Hung
authors.initials: HH
authors.lastname: Chen
authors.forename: Max T
authors.initials: MT
authors.lastname: Huang
authors.forename: Chao-Yuh
authors.initials: CY
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002417:Cattle; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D008078:Cholesterol, LDL / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism*; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D008078:Cholesterol, LDL