Smooth Muscle-Specific SM22 Protein Is Expressed in the Adventitial Cells of Balloon-Injured Rabbit Carotid Artery

Abstract

Abstract-During 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-deoxyuridine-positive 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. (Arterioscler Thromb Vasc Biol.

Origin of periendothelial cells in microvessels derived from human microvascular endothelial cells

“…It is possible that fibroblasts present within the connective tissue in vivo not only maintain ECM and connective tissue homeostasis, but also serve as tissue-resident progenitors of skin-associated lineages. Fibroblasts appear to serve as vascular cell progenitors in the injured rabbit carotid artery (Faggin et al, 1999). Large blood vessels, such as the carotid artery, are composed of three distinct layers of tissue, the intima, media, and adventitia.…”

Deficiency of Interleukin-1 Receptor Antagonist Promotes Neointimal Formation After Injury

“…Recent studies have shown that adventitial passive fibroblasts can become active myofibroblasts under conditions of adventitial inflammation. 10,11 On the other hand, SMCs were the predominant proliferating cell type in the intima. IL-1 itself is mitogen for SMCs, 1 and furthermore, a recent study showed that vascular intima formation after mechanical injury was found to consist mainly of inflammation-associated cells that originated from the bone marrow.…”

Mechanisms of Neointima Formation and Remodeling in the Porcine Coronary Artery

“…They are in agreement with current views concerning the pathogenesis of stent-induced lesions, 8 whereas the pathogenesis of PTCA-induced lesions has up to now remained controversial. 6,7,[15][16][17] …”

“…16 When fibroblasts transduced with retroviral particles encoding ␤-galactosidase were implanted in the adventitia of the rat carotid artery, some of these cells could be found in neointima formation after balloon injury. 17 The relative proportions of SMCs and fibroblasts participating in neointima formation in that model remain to be established.…”