期刊
JOURNAL OF VASCULAR SURGERY
卷 51, 期 2, 页码 417-428出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jvs.2009.09.004
关键词
-
资金
- Institute de l'Atherothrombose France
- Institut de France-Fondation Lefoulon Delalande
Objective: The introduction of drug-eluting stents (DES) has largely added benefit to the percutaneous coronary intervention. Questions about the long-term safety of DES have been raised, however, particularly with respect to late stent thrombosis. Research efforts are now being directed toward therapeutics that call impede smooth muscle proliferation and promote vascular healing. Emerging data suggest that heme oxygenase-1 (HO-1), ail inducible oxidoreductase enzyme system, call exert cytoprotective effects oil endothelial cells and limit smooth muscle cell proliferation. We assessed the ability of hemin,a potent HO-1 inducer, to reduce in-stent stenosis without compromising re-endothelialization. Methods: Rat aorta and rabbit iliac arteries were stented. Animals received ongoing treated with intraperitoneal hemin (50 mg/kg) or vehicle. At 7 to 28 days after surgery, stented arterial segments were collected and processed for histologic, electron microscopy, or protein analysis. Results: In both models, treatment with hemin reduced neointima growth without compromising re-endothelialization of the stented arteries. In the rat aorta, analysis of protein expression at 7 and 28 days after stenting revealed that hemin increased HO-1 expression and limited the early inflammatory, apoptotic, and proliferative cellular events that are common to in-stent stenosis. Hemin treatment decreased the expression of the Ki-67 protein mid the activity of key regulators of smooth muscle cell proliferation, including p42/44, RhoA, and up-regulated the expression of cyclin-dependent kinase inhibitors. The beneficial effects of hemin were abolished in the presence of tin-protoporphyrin IX, an HO inhibitor. Finally, treatment with tricarbonylchloro(glycinato)ruthenium(II), a carbon monoxide donor, reduced in-stent stenosis in the rat aorta, suggesting that carbon monoxide, a by-product of heme degradation, might contribute to the protective effect of hemin. Conclusion: These results suggest that HO-1 is important in limiting in-stent stenosis and call be regarded as a new therapeutic target. (J Vasc Surg 2010;51:417-28.)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据