Angiotensin II type 1 receptor blockade attenuates in-stent restenosis by inhibiting inflammation and progenitor cells
Angiotensin II type 1 receptor blockade attenuates in-stent restenosis by inhibiting inflammation and progenitor cells
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DOI：
10.1161/01.hyp.0000237974.74488.30
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发表时间：
2006-10-01
期刊：
影响因子：
8.3
通讯作者：
Sunagawa, Kenji
中科院分区：
文献类型：
--
作者：
Ohtani, Kisho;Egashira, Kensuke;Sunagawa, Kenji
在临床试验中，血管紧张素11 I型受体阻滞剂减少支架内再狭窄的确切机制尚不清楚。因此，我们研究了支架内新生内膜形成的机制。雄性食蟹猴和家兔喂食高胆固醇饲料，并分配至未给药对照组和I型受体阻滞剂组。分组后5天，在髂动脉中植入Multilink支架。在家兔和猴中，I型受体阻滞剂可将支架内新生内膜形成的发生减少约30%。为了研究潜在的机制，我们检测了肾素-血管紧张素系统标志物的表达，所有这些标志物在7天内在新生内膜和中膜的单核细胞和平滑肌样细胞中均增加。I型受体阻滞剂减弱了氧化应激的增加，增强了肾素-血管紧张素系统和单核细胞趋化蛋白-1的标记物的表达，以及巨噬细胞浸润。同时观察I型受体阻滞剂对外周血单个核细胞向血管祖细胞分化的影响。用I型受体阻滞剂治疗抑制了支架植入诱导的向平滑肌祖细胞的分化增强。I型受体阻滞剂通过抑制氧化还原敏感性炎症变化和减少祖细胞的募集来减弱支架内新生内膜的形成。I型受体阻滞剂对炎症和祖细胞的这些潜在作用构成了I型受体阻滞剂抑制支架内再狭窄的新机制。
The precise mechanism by which angiotensin 11 type I receptor blocker reduces in-stent restenosis in clinical trials is unclear. We, therefore, investigated the mechanism of in-stent neointima formation. Male cynomolgus monkeys and rabbits were fed a high-cholesterol diet and were allocated to untreated control and type I receptor blocker groups. Five days after grouping, multilink stents, were implanted in the iliac artery. The type I receptor blocker reduced the development of in-stent neointima formation by approximate to 30% in rabbits and monkeys. To investigate potential mechanisms, we examined the expression of renin-angiotensin system markers, all of which increased in monocytes and smooth muscle-like cells in the neointima and media within 7 days. The type I receptor blocker attenuated increased oxidative stress, the enhanced expression of markers of the rennin-angiotensin system and monocyte chemoattractant protein-1, and macrophage infiltration. The effects of type I receptor blocker on the differentiation of peripheral blood mononuclear cells into vascular progenitor cells were also examined. Treatment with type I receptor blocker suppressed the enhanced differentiation to smooth muscle progenitor cells induced by stenting. The type I receptor blocker attenuated in-stent neointima formation by inhibiting redox-sensitive inflammatory changes and by reducing recruitment of the progenitor cells. These potential actions of type I receptor blocker on inflammation and progenitor cells constitute a novel mechanism of suppression of in-stent restenosis by type I receptor blocker.