Smoothelin is an indicator of reversible phenotype modulation of smooth muscle cells in balloon-injured rat carotid arteries
Smoothelin is an indicator of reversible phenotype modulation of smooth muscle cells in balloon-injured rat carotid arteries
复制标题
DOI：
10.1007/s395-002-8382-z
复制
发表时间：
2002-01-01
影响因子：
9.5
通讯作者：
Jahn, L
中科院分区：
文献类型：
--
作者：
Bär, H;Wende, P;Jahn, L
再狭窄是影响球囊血管成形术成功的长期结果的主要障碍。内皮损伤后新内膜的形成是平滑肌细胞（SMC）表型调节和增殖的结果。为了表征这些时间依赖性变化，评估了颈动脉再狭窄的大鼠球囊损伤模型。我们应用了识别结蛋白、sm-α-肌动蛋白和 smoothelin（一种针对 SMC 分化表型的新型标记物）的单克隆抗体。从损伤后第 7 天开始就可以看到新内膜形成。在早期阶段，与未受伤的对照相比，培养基中平滑蛋白阳性细胞的数量减少。在形成过程中，新内膜中不存在平滑蛋白染色。在第 28 天和第 56 天观察到中膜和新内膜中平滑蛋白水平增加，这与通过 Ki-67 抗原染色评估的增殖减少相关。结蛋白和 sm-α-肌动蛋白没有观察到这种变化。球囊损伤后，中膜和新内膜中的 SMC 经历了早期、可逆的去分化，随后发生增殖。新型 SMC 特异性标记蛋白 smoothelin 可用于监测新内膜和中膜中的 SMC (de) 分化。这些发现支持 SMC 表型调节在新内膜形成和再狭窄中的关键作用。
Restenosis is the major obstacle interfering with a successful long-term outcome of balloon angioplasty. Neointima formation following endothelial injury is the result of phenotype modulation and proliferation of smooth muscle cells (SMC). To characterize these time-dependent changes, a rat balloon injury model of carotid artery restenosis was assessed. We applied monoclonal antibodies recognizing desmin, sm-alpha-actin and smoothelin, a novel marker specific for the differentiated phenotype of SMC.Neointima formation could be seen from day 7 after injury onwards. During early phases, the number of smoothelin-positive cells in the media was decreased compared with uninjured controls. Smoothelin staining was absent in the neointima during formation. Increased levels of smoothelin in both media and neointima were observed at days 28 and 56, correlating with a decrease in proliferation as assessed by Ki-67 antigen staining. No such changes were observed for desmin and sm-alpha-actin.Following balloon injury, SMC in both the media and the neointima underwent an early, reversible dedifferentiation, followed by proliferation. The novel SMC-specific marker protein smoothelin can be used to monitor this SMC (de) differentiation in neointima and media. These findings support the pivotal role of SMC phenotype modulation in neointima formation and restenosis.