level in intact rat aortic SMCs, whereas NPR-B is expressed
predominantly in cultured cells . It can be hypothesized
that the more potent action of CNP relates to the phenotype-
related expression of natriuretic receptors. However, NPR-A
and NPR-B mRNA expression measured by RT-PCR did not
differ betw een injured and intact rat carotid arteries. These
results do not support the concept that ANP NPR-A
markedly decreases after de-endothelialization, as reported
previously in a rabbit model of injury caused by compression
differences in the animal model or experimental conditions.
An alternative explanation for the more potent action of
CNP may be the higher binding afﬁnity of the clearance
receptor NPR-C to ANP, as demonstrated by Suga et al.
. It is possible that, in the present study, the in vivo
effects of ANP were limited by its short half-life.
Furthermore, a complete re-endothelialization was
observed 2 weeks after injury in all Ad-RSV-ANP treated
arteries, as well as in control groups, suggesting that inhibi-
tion of neointima formation by this approach did not com-
promise endothelial repair. This ﬁnding could have an inter-
est in the prevention of restenosis or stent thrombosis
In summary, the ﬁndings of the present study demon-
strate that the recombinant adenovirus Ad-RSV-ANP is
an effective tool for modulating SMC proliferation and
migration. The results obtained in the de-endothelialized
rat carotid arter y provide evidence that ANP plays a
protective role against changes in proliferation and
migration in vivo in the injured artery. Adenovirus-mediated
local expression of ANP has potential as an effective form
of molecular intervention in proliferative arterial diseases.
The authors declare that there are no conﬂicts of interest.
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