Vascular Biology |
From the Departments of Experimental and Clinical Medicine (E.F., M.P., P.P.) and Biomedical Sciences (A.C., C.M., F.S., L.Z., R.F., S.S.), University of Padua, and the CNR Unit for Muscle Biology and Physiopathology (S.S.), Padua, Italy.
Correspondence to Angela Chiavegato, PhD, Department of Biomedical Sciences, University of Padua, Viale G Colombo, 3, I-35121 Padua, Italy. E-mail smggroup{at}civ.bio.unipd.it
AbstractDuring the
"response-to-injury" process after a mechanical insult to the
porcine coronary arteries, the adventitial cells acquire the
structural characteristics of myofibroblasts before being incorporated
into smooth muscle (SM) layer. We assessed whether the SM-specific SM22
protein can be used as a tracer of adventitial cell-myofibroblast
differentiation in the mild balloon injury of rabbit carotid artery. To
achieve this goal, we used 2 monoclonal anti-SM22 antibodies (E-11 and
1-B8) and a molecular probe for the SM22
mRNA isoform in
immunocytochemical and in situ hybridization experiments. The
differentiation profile and the migratory and proliferative ability of
activated adventitial cells were evaluated by a panel of
antibodies to some SM and nonmuscle antigens and pulse- and
end-labeling with bromo-deoxyuridine, respectively. In adventitial
cells, SM22 antigenicity and SM22
mRNA were detectable at days 2 and
4 and, to a lesser extent, at days 7 and 21 after injury, particularly
near the adventitia-media interface and mostly colocalizing with
bromo-deoxyuridinepositive cells. The pulse-labeling experiments
showed that the large majority of these cells penetrated the outermost
layer of the tunica media without migrating to the
subendothelial region. The phenotypic features of
activated migrating and nonmigrating adventitial cells
resembled those of vimentin-actin myofibroblast subtype and fetal-type
SM cells. These findings indicate that a direct exposure of adventitia
to the lumen is not required for phenotypic changes and
proliferation/migration of these cells. After comparison of the SM22
expression in arterial vessels during early stages of
development, we hypothesize that in the injured carotid artery the
mural incorporation of adventitial cells and the spatiotemporal
activation of SM22 expression are reminiscent of the vascular
morphogenetic process and suggest the existence of a stem cell-like
reservoir in adventitia. The early adventitial upregulation of SM22
expression in the injured vessel might be related to a multistep
transition process in which nonmuscle cells are converted to
myofibroblasts and, possibly, to SM cells.
Key Words: smooth muscle cell adventitia differentiation endothelial injury SM22
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