Doxycycline alters vascular smooth muscle cell adhesion, migration, and reorganization of fibrillar collagen matrices
Doxycycline alters vascular smooth muscle cell adhesion, migration, and reorganization of fibrillar collagen matrices
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DOI：
10.2353/ajpath.2006.050613
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发表时间：
2006-05-01
影响因子：
6
通讯作者：
Bendeck, MP
中科院分区：
文献类型：
--
作者：
Franco, C;Ho, B;Bendeck, MP
损伤血管的重塑依赖于平滑肌细胞和基质金属蛋白酶活性。多西环素是一种广谱基质金属蛋白酶抑制剂，正在研究用于治疗急性冠状动脉综合征和动脉瘤。在本研究中，我们研究了多西环素抑制平滑肌细胞反应的机制，采用一系列体外试验，模拟病理性血管重塑的关键步骤。强力霉素治疗显着增加平滑肌细胞粘附到基板上，所证明的干扰反射显微镜和桩蛋白和磷酸酪氨酸的免疫染色。用强力霉素处理后，细胞聚集也增强。104 μ mol/L多西环素处理使胸苷摄取减少58%（P < 0.05），使平滑肌细胞单层刮伤闭合抑制20%（P < 0.05）。三维胶原凝胶的收缩被用作收缩性血管重塑的体外模型，证明用416 Nmol/L多西环素处理12小时相对于对照抑制胶原凝胶重塑37%（P < 0.05）。总之，我们已经表明，强力霉素治疗导致平滑肌细胞粘附显着增加，这反过来可能会限制病理性血管重塑的反应。
Remodeling of injured blood vessels is dependent on smooth muscle cells and matrix metalloproteinase activity. Doxycycline is a broad spectrum matrix metalloproteinase inhibitor that is under investigation for the treatment of acute coronary syndromes and aneurysms. In the present study, we examine the mechanisms by which doxycycline inhibits smooth muscle cell responses using a series of in vitro assays that mimic critical steps in pathological vascular remodeling. Doxycycline treatment dramatically increased smooth muscle cell adhesion to the substrate, as evidenced by interference reflection microscopy and immunostaining for paxillin and phosphotyrosine. Cell aggregation was also potentiated after treatment with doxycycline. Treatment with 104 mu mol/L doxycycline reduced thymidine uptake by 58% compared with untreated cells (P < 0.05) and inhibited closure of a scrape wound made in a smooth muscle cell monolayer by 20% (P < 0.05). Contraction of a three-dimensional collagen gel was used as an in vitro model for constrictive vessel remodeling, demonstrating that treatment with 416 Nmol/L doxycycline for 12 hours inhibited collagen gel remodeling by 37% relative to control (P < 0.05). In conclusion, we have shown that doxycycline treatment leads to dramatically increased smooth muscle cell adhesion, which in turn might limit responses in pathological vascular remodeling.