First 11 pages of thesis. - OPUS - Universität Würzburg

Transient gene transfer mediated expression of iNOS decreases smooth
muscle cell proliferation and prevents neointima formation following balloon
angioplasty in rats and pigs 170 . The same authors reported that iNOS gene
transfer protects aortic allografts from developing allograft arteriosclerosis 171 . In
mice, iNOS protects from developing transplant arteriosclerosis by inhibiting
neointimal smooth muscle accumulation 172 . Another recent study showed that
iNOS prevents vein graft arteriosclerosis by inhibiting vascular smooth muscle
cell proliferation 173 and neointimal hyperplasia 174 .
In vitro, iNOS ko mice show an improved cardiac reserve following
myocardial infarction which was thought to be necessary to the reduction in
oxidative stress seen in this model 175 . Genetic deletion of iNOS gene also led
to partial protection against acute cardiac mechanical dysfunction mediated by
pro-inflammatory cytokines 176 . The expression of iNOS is considered to be
responsible for impairment of eNOS derived nitric oxide production in vessels
treated with inflammatory mediators 177 . Further studies suggest that iNOS plays
an important role in the impairment of endothelium dependent vascular
relaxation, which may occur in part by limiting cofactor availability (BH4) and
subsequent eNOS uncoupling 178 . The expression of iNOS by macrophages and
smooth muscle cells in atherosclerotic lesions has been taken as evidence for
its detrimental role in atherosclerosis, due to formation of peroxynitrite 179 . We
and others have shown that genetic deletion of iNOS resulted in a significant
reduction of lesion formation in apoE ko mice, documenting the proatherogenic
potential of iNOS 180, 181 . Our results were reconfirmed by Hayashi et al. who
showed that selective pharmacological inhibition of iNOS results in retardation
of atherosclerosis in rabbits 182 .
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