Db. Schneider et al., Expression of Fas ligand in arteries of hypercholesterolemic rabbits accelerates atherosclerotic lesion formation, ART THROM V, 20(2), 2000, pp. 298-308
Fas ligand (FasL) is expressed by cells of the arterial wall and is present
in human atherosclerotic lesions. However, the role of Fast in modifying t
he initiation and progression of atherosclerosis is unclear. To investigate
the role of arterial Fast expression in the development of atherosclerosis
, we first established a model of primary lesion formation in rabbit caroti
d arteries. In this model, infusion of adenoviral vectors into surgically i
solated, nondenuded arteries of hypercholesterolemic rabbits leads to the f
ormation of humanlike early atherosclerotic lesions. Expression of Fast in
arterial endothelium in this model decreased T-cell infiltration and expres
sion of vascular cell adhesion molecule-1 but did not affect expression of
intercellular adhesion molecule-1. Intimal lesions grew more rapidly in Fas
L-transduced arteries than in arteries transduced with a control adenovirus
that did not express a transgene. Total intimal macrophage accumulation wa
s increased in FasL-transduced arteries, however, the proportion of lesion
area occupied by macrophages was not elevated. The accelerated lesion growt
h 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 Fast expression is to accelerate atheroscleroti
c lesion growth by increasing lesion cellularity. Vascular expression of Fa
st may contribute to the progression of atherosclerosis.