Changes in perlecan expression during vascular injury - Role in the inhibition of smooth muscle cell proliferation in the late lesion
Changes in perlecan expression during vascular injury - Role in the inhibition of smooth muscle cell proliferation in the late lesion
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DOI：
10.1161/01.atv.0000063109.94810.ee
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发表时间：
2003-04-01
影响因子：
8.7
通讯作者：
Wight, TN
中科院分区：
文献类型：
--
作者：
Kinsella, MG;Tran, PK;Wight, TN
目的：血管平滑肌细胞（vascular smooth muscle cells, SMCs）在动脉损伤后，在生长因子的激活下迁移、增殖，扩张血管内膜。在内膜扩张过程中，增殖受到抑制，新内膜肿块由新合成的细胞外基质（ECM）组成的比例越来越大。我们试图确定体外抑制SMC增殖的ECM硫酸肝素蛋白聚糖（HSPG） perlecan是否也在内膜扩张过程中积累并限制SMC增殖。方法与结果：应用免疫组织化学和原位杂交技术分析大鼠颈动脉球囊导管损伤后新内膜形成过程中perlecan的表达和积累。Perlecan在未损伤血管中的表达较低，在损伤后7天内，也就是SMC增殖最大的时候。损伤后14天，perlecan显著增加，在损伤后35至42天的晚期病变中，免疫染色仍然很重。最后，用糖胺聚糖酶消化35- 42天新生内膜病变的内膜组织，以确定内源性HSPGs是否抑制内膜SMC增殖。在hs耗尽的SMCs中，而不是在软骨素酶abc处理或模拟培养的SMCs中，外植体对血小板衍生生长因子BB有增殖反应。结论- hspgs，如perlecan，可能抑制血管损伤后SMCs的增殖反应。
Objective-Vascular smooth muscle cells (SMCs), activated by growth factors after arterial injury, migrate and proliferate to expand the intima of the blood vessel. During intimal expansion, proliferation is suppressed and an increasingly large proportion of the neointimal mass is composed of newly synthesized extracellular matrix (ECM). We sough to determine whether the ECM heparan sulfate proteoglycan (HSPG) perlecan, which inhibits SMC proliferation in vitro, also accumulates and limits SMC proliferation during neointimal expansion.Methods and Results-Perlecan expression and accumulation were analyzed by immunohistochemistry and in situ hybridization during neointima formation after balloon catheter injury to the rat carotid artery. Perlecan expression was low in uninjured vessels and up to 7 days after injury, during maximal SMC proliferation. By 14 days after injury, perlecan was dramatically increased, and immunostaining remained heavy throughout the advanced lesion, 35 to 42 days after injury. Finally, explants of intimal tissue from 35- to 42-day neointimal lesions were digested with glycosaminoglycanases to determine whether endogenous HSPGs inhibit intimal SMC proliferation. SMCs within HS-depleted, but not chondroitinase ABC-treated or mock-incubated, explants were found to proliferate in response to platelet-derived growth factor BB.Conclusions-HSPGs, such as perlecan, may inhibit the proliferative response of SMCs after vascular injury.