Expression of Fas ligand in arteries of hypercholesterolemic rabbits accelerates atherosclerotic lesion formation
Details
Serval ID
serval:BIB_2C9031AA916E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Expression of Fas ligand in arteries of hypercholesterolemic rabbits accelerates atherosclerotic lesion formation
Journal
Arteriosclerosis, Thrombosis, and Vascular Biology
ISSN
1079-5642 (Print)
Publication state
Published
Issued date
02/2000
Volume
20
Number
2
Pages
298-308
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Feb
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Feb
Abstract
Fas ligand (FasL) is expressed by cells of the arterial wall and is present in human atherosclerotic lesions. However, the role of FasL in modifying the initiation and progression of atherosclerosis is unclear. To investigate the role of arterial FasL expression in the development of atherosclerosis, we first established a model of primary lesion formation in rabbit carotid arteries. In this model, infusion of adenoviral vectors into surgically isolated, nondenuded arteries of hypercholesterolemic rabbits leads to the formation of human-like early atherosclerotic lesions. Expression of FasL in arterial endothelium in this model decreased T-cell infiltration and expression of vascular cell adhesion molecule-1 but did not affect expression of intercellular adhesion molecule-1. Intimal lesions grew more rapidly in FasL-transduced arteries than in arteries transduced with a control adenovirus that did not express a transgene. Total intimal macrophage accumulation was increased in FasL-transduced arteries; however, the proportion of lesion area occupied by macrophages was not elevated. The accelerated lesion growth was primarily due to the accumulation of intimal smooth muscle cells with a synthetic proliferative phenotype. There was no significant apoptosis in FasL-transduced or control arteries and no granulocytic infiltrates. Thus, the net result of elevated FasL expression is to accelerate atherosclerotic lesion growth by increasing lesion cellularity. Vascular expression of FasL may contribute to the progression of atherosclerosis.
Keywords
Adenoviridae/physiology
Animals
Apoptosis/physiology
Arteries/*metabolism
Arteriosclerosis/*etiology/metabolism/pathology
Cell Division/drug effects
Endothelium, Vascular/metabolism
Fas Ligand Protein
Gene Expression
Hypercholesterolemia/*complications/*metabolism
Macrophages/pathology
Membrane Glycoproteins/genetics/*metabolism/pharmacology
Muscle, Smooth, Vascular/cytology/drug effects/physiology
Rabbits
T-Lymphocytes/physiology
Transgenes/genetics
Vascular Cell Adhesion Molecule-1/metabolism
Pubmed
Web of science
Create date
28/01/2008 10:32
Last modification date
20/08/2019 13:11