Insulin-like growth factor-1 protects from vascular stenosis and accelerates re-endothelialization in a rat model of carotid artery injury
Insulin-like growth factor-1 protects from vascular stenosis and accelerates re-endothelialization in a rat model of carotid artery injury
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DOI：
10.1111/j.1538-7836.2009.03607.x
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发表时间：
2009-11-01
影响因子：
10.4
通讯作者：
Sacca, L.
中科院分区：
文献类型：
--
作者：
Cittadini, A.;Monti, M. G.;Sacca, L.
背景：IGF-1 是血管平滑肌细胞的有效有丝分裂原，但对内皮细胞发挥保护作用，可能触发抗动脉粥样硬化机制。目的：本研究旨在检验动脉损伤后 IGF-1 过量可防止新内膜形成和血管狭窄的假设。方法：对大鼠进行颈动脉球囊损伤，并用 IGF-1（每只小鼠 1.2 mg kg-1）或生理盐水治疗 10 天。结果：在 IGF-1 治疗的动物中，发现了高组织水平的 eNOS、Akt 及其磷酸化形式，证实了 IGF-1 依赖性信号通路的激活。 IGF-1 显着减少新内膜形成和损伤后动脉狭窄。 IGF-1 在受损颈动脉中层发挥增殖和抗凋亡作用，但在新内膜中抑制有丝分裂活性并诱导细胞凋亡。此外，IGF-1 刺激祖内皮细胞的动员和受损动脉的重新内皮化。 L-NAME 给药抑制 IGF-1 血管保护作用。结论：IGF-1 通过在新内膜和中膜中对损伤反应的关键成分发挥不同作用来减轻损伤后颈动脉狭窄。这些数据表明 IGF-1 作为有效的血管保护因子的新作用。
Background: IGF-1 is a potent mitogen for vascular smooth muscle cells, but exerts protective effects on endothelial cells that may trigger antiatherogenic mechanisms. Objectives: This study was designed to test the hypothesis that an IGF-1 excess following arterial injury prevents neointima formation and vascular stenosis. Methods: Rats were subjected to carotid balloon injury and treated with IGF-1 (1.2 mg kg-1 per die) or saline for 10 days. Results: In IGF-1 treated animals, high tissue levels of eNOS, Akt and its phosphorylated form were found, confirming activation of IGF-1-dependent signaling pathways. IGF-1 markedly reduced neointima formation and post-injury arterial stenosis. IGF-1 exerted proliferative and anti-apoptotic effects in the media of injured carotids, but inhibited mitotic activity and induced apoptosis in the neointima. Furthermore, IGF-1 stimulated mobilization of progenitor endothelial cells and re-endothelialization of the injured arteries. L-NAME administration inhibited IGF-1 vasculoprotective effects. Conclusions: IGF-1 attenuates post-injury carotid stenosis by exerting differential effects in the neointima and tunica media with regard to the key components of the response to injury. The data point to a novel role of IGF-1 as a potent vasculoprotective factor.