title: Expression of Fas ligand in arteries of hypercholesterolemic rabbits accelerates atherosclerotic lesion formation.
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.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, University of California, San Francisco 94141-9100, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Schneider
authors.forename: G
authors.initials: G
authors.lastname: Vassalli
authors.forename: S
authors.initials: S
authors.lastname: Wen
authors.forename: R M
authors.initials: RM
authors.lastname: Driscoll
authors.forename: A B
authors.initials: AB
authors.lastname: Sassani
authors.forename: M B
authors.initials: MB
authors.lastname: DeYoung
authors.forename: R
authors.initials: R
authors.lastname: Linnemann
authors.forename: R
authors.initials: R
authors.lastname: Virmani
authors.forename: D A
authors.initials: DA
authors.lastname: Dichek
mesh_terms: D000256:Adenoviridae / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001158:Arteries / Q000378:metabolism*; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism; D053222:Fas Ligand Protein; D015870:Gene Expression; D006937:Hypercholesterolemia / Q000150:complications* / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D013601:T-Lymphocytes / Q000502:physiology; D019076:Transgenes / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019010:Vascular Cell Adhesion Molecule-1