Identification of a potential role for the adventitia in vascular lesion formation after balloon overstretch injury of porcine coronary arteries
Identification of a potential role for the adventitia in vascular lesion formation after balloon overstretch injury of porcine coronary arteries
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DOI：
10.1161/01.cir.93.12.2178
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发表时间：
1996-06-15
期刊：
影响因子：
37.8
通讯作者：
Wilcox, JN
中科院分区：
文献类型：
--
作者：
Scott, NA;Cipolla, GD;Wilcox, JN
背景在目前的一系列实验中，我们研究了发病后的细胞增殖和生长因子的表达球囊过度拉伸损伤猪冠状动脉。方法和结果国内少年猪进行球囊过度拉伸损伤左前降支和回旋冠状动脉与标准经皮冠状动脉腔内成形术球囊导管。为了鉴定增殖细胞，在损伤后1、3、7或14天处死动物之前，在24小时内施用5-溴-2-脱氧尿苷（BrDU）。用抗BrDU单克隆抗体和平滑肌细胞标记物进行免疫组化。损伤后3天，大量增殖细胞位于外膜，中膜和管腔中的阳性细胞明显减少。损伤后7天，主要在新生内膜中发现增殖细胞，其沿着管腔表面延伸。PDGF A链和β受体mRNA的原位杂交显示，这两个基因的表达与每个时间点的增殖部位密切相关。研究中，BrDU注射之间的第2和3天，动物被杀死的第14天表明，增殖的外膜细胞可能迁移到neointima.Conclusions这些数据表明，外膜肌成纤维细胞有助于血管病变的形成过程中增殖，合成生长因子，并可能迁移到neointima。在动脉损伤后的外膜细胞中观察到的α-平滑肌肌动蛋白的合成增加可能收缩损伤的血管，并有助于血管成形术后的动脉重塑和晚期管腔丢失的过程。
Background In the present series of experiments, we examined the onset of cell proliferation and growth factor expression after balloon overstretch injury to porcine coronary arteries.Methods and Results Domestic juvenile swine underwent balloon overstretch injury to the left anterior descending and circumflex coronary arteries with standard percutaneous transluminal coronary angioplasty balloon catheters. To identify proliferating cells, 5-bromo-2-deoxyuridine (BrDU) was administered over a period of 24 hours before the animals were killed at either 1, 3, 7, or 14 days after injury. Immunohistochemistry was performed with monoclonal antibodies to BrDU and smooth muscle cell markers. Three days after injury, a large number of proliferating cells were located in the adventitia, with significantly fewer positive cells found in the media and lumen. Seven days after injury, proliferating cells were found primarily in the neointima, extending along the luminal surface. In situ hybridization for PDGF A-chain and beta-receptor mRNAs revealed that the expression of these two genes was closely correlated with the sites of proliferation at each lime point. Studies in which BrDU was injected between days 2 and 3 and the animals were killed on day 14 suggested that the proliferating adventitial cells may migrate into the neointima.Conclusions These data suggest that adventitial myofibroblasts contribute to the process of vascular lesion formation by proliferating, synthesizing growth factors, and possibly migrating into the neointima. Increased synthesis of alpha-smooth muscle actin observed in the adventitial cells after arterial injury may constrict the injured vessel and contribute to the process of arterial remodeling and late lumen loss after angioplasty.