Proliferating arterial smooth muscle cells after balloon injury express TNF-alpha but not interleukin-1 or basic fibroblast growth factor
Proliferating arterial smooth muscle cells after balloon injury express TNF-alpha but not interleukin-1 or basic fibroblast growth factor
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DOI：
10.1161/01.atv.16.1.12
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发表时间：
1996-01-01
影响因子：
8.7
通讯作者：
Libby, P
中科院分区：
文献类型：
--
作者：
Tanaka, H;Sukhova, G;Libby, P
我们最近报道了兔腹主动脉球囊提取损伤诱导持续激活，这表明再生内皮细胞和/或增殖平滑肌细胞（SMCs）中某些粘附分子（如血管细胞粘附分子-1和细胞间粘附分子-1）的表达。局部细胞因子信号可能有助于急性血管损伤后细胞功能的持续调节和内膜SMCs的增殖。因此，我们在球囊损伤后2 （n=4）、5 （n=4）和10 （n=6）天研究了兔主动脉SMCs中肿瘤坏死因子- α (tnf - α)和白细胞介素-1 β (IL-1 β)、促炎因子和促SMC生长因子以及碱性成纤维细胞生长因子（bFGF）的表达。所有动物连续给予溴脱氧尿嘧啶（BrdU, 10 mg/kg / d）标记增殖的SMCs。单克隆抗体免疫过氧化物酶染色检测球囊损伤后各时间点损伤血管的冰冻截面。早在损伤后2天，在内膜增厚开始之前，内侧SMCs的病灶就表达了tnf - α，但并非所有tnf - α阳性的内侧SMCs都合并了BrdU，这表明内侧SMCs可能在增殖之前就表达了tnf - α。第5天，携带tnf - α和brdu标记的内侧SMCs数量增加。在损伤后10天，当均匀的内膜增厚发生时，几乎所有的新内膜间充质干细胞和内侧间充质干细胞灶都标记有BrdU。大多数brdu阳性（增殖）的SMCs表达免疫反应性tnf - α。逆转录聚合酶链反应显示，在主动脉损伤部位肿胀10天后，tnf - α mRNA升高。相比之下，SMC增殖区域IL-1 β表达不一致，正常兔动脉中丰富的bFGF在SMC复制区域未检测到。这些数据表明，球囊损伤后动脉SMCs的复制发生在tnf - α表达区，而不是IL-1 β表达区，并且与bFGF的存在呈负相关。这些结果表明，SMC来源的tnf - α作为急性血管损伤后SMC表型调节的标志，可能有助于动脉损伤部位SMC的局部细胞活化和增殖。
We have recently reported that balloon withdrawal injury to rabbit abdominal aortas induces sustained activation indicated by the expression of certain adhesion molecules such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in regenerating endothelial cells and/or proliferating smooth muscle cells (SMCs). Local cytokine signaling may contribute to ongoing modulation of cellular functions and proliferation of intimal SMCs after acute vascular injury. We therefore studied the expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), proinflammatory and SMC growth-promoting cytokines, and basic fibroblast growth factor (bFGF) in SMCs of rabbit aorta at 2 (n=4), 5 (n=4), and 10 days (n=6) after balloon injury. All animals were given bromodeoxyuridine (BrdU, 10 mg/kg per day) continuously to label proliferating SMCs. Frozen cross sections of injured vessels at each time point after balloon injury were examined by immunoperoxidase staining with monoclonal antibodies. As early as 2 days after injury, before intimal thickening begins, foci of medial SMCs expressed TNF-alpha, but not all TNF-alpha-positive medial SMCs had incorporated BrdU, suggesting that TNF-alpha expression by medial SMCs may precede their proliferation. Al 5 days, TNF-alpha-bearing and BrdU-labeled medial SMCs increased in number. At 10 days after injury, when uniform intimal thickening occurred, almost all neointimal SMCs and foci of medial SMCs labeled with BrdU. Most of the BrdU-positive (proliferating) SMCs expressed immunoreactive TNF-alpha. Reverse transcription polymerase chain reaction showed increased TNF-alpha mRNA at 10 days after ballooning in the injured portion of the aorta. In contrast, regions of SMC proliferation showed inconsistent IL-1 beta expression, and bFGF, abundant in normal rabbit arteries, was not detected in areas of SMC replication. These data indicate that replication of arterial SMCs after balloon injury occurs in regions of TNF-alpha but not IL-1 beta expression and correlates inversely with the presence of bFGF. These results indicate that SMC-derived TNF-alpha serves as a marker of modulated SMC phenotype after acute vascular injury and may contribute to local cellular activation and proliferation of SMCs at sites of arterial injury.