Smooth muscle-specific SM22 protein is expressed in the adventitial cells of balloon-injured rabbit carotid artery
Smooth muscle-specific SM22 protein is expressed in the adventitial cells of balloon-injured rabbit carotid artery
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DOI：
10.1161/01.atv.19.6.1393
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发表时间：
1999-06-01
影响因子：
8.7
通讯作者：
Chiavegato, A
中科院分区：
文献类型：
--
作者：
Faggin, E;Puato, M;Chiavegato, A
在猪冠状动脉机械损伤后的“对损伤的反应”过程中，外膜细胞在并入平滑肌（SM）层之前获得肌成纤维细胞的结构特征。我们评估了SM特异性SM 22蛋白是否可以用作兔颈动脉轻度球囊损伤中外膜细胞-肌成纤维细胞分化的示踪剂。为了实现这一目标，我们在免疫细胞化学和原位杂交实验中使用了2种单克隆抗SM 22抗体（E-II和1-B8）和SM 22 α mRNA同种型的分子探针。通过一组针对一些SM和非肌肉抗原的抗体以及分别用溴脱氧尿苷进行脉冲和末端标记来评价活化的外膜细胞的分化概况和迁移和增殖能力。在外膜细胞中，SM 22抗原性和SM 22 a mRNA在损伤后第2天和第4天可检测到，在较小程度上，在损伤后第7天和第21天可检测到，特别是在外膜-中膜界面附近，并且主要与溴脱氧尿苷阳性细胞共定位。脉冲标记实验表明，这些细胞的绝大多数穿透最外层的图尼卡中膜没有迁移到内皮下区域。活化的迁移和非迁移外膜细胞的表型特征类似于波形蛋白肌动蛋白肌成纤维细胞亚型和胎儿型SM细胞的表型特征。这些结果表明，这些细胞的表型变化和增殖/迁移不需要外膜直接暴露于管腔。在比较了发育早期动脉血管中的SM 22表达后，我们假设在受损的颈动脉中，外膜细胞的壁掺入和SM 22表达的时空激活使人联想到血管形态发生过程，并表明外膜中存在干细胞样储库，损伤血管中SM 22表达的早期外膜上调可能与非肌细胞转化为肌成纤维细胞和可能转化为SM细胞的多步过渡过程有关。
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-ll and 1-B8) and a molecular probe for the SM22 alpha 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 SM22a 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.