JCI:动脉粥样硬化中抑制IL-1面临是否有利的问题
2012-01-01 MedSci原创 MedSci原创
据2011年12月27日《医学快线》报道,动脉粥样硬化是重要的动脉血管疾病,它是导致心脏病和中风的主要原因之一。 促炎性分子IL-1与动脉粥样硬化有关,目前已启动了一项临床试验,在该项临床试验中,一种针对IL-1β的特异性抗体被用于研究它在严重的动脉粥样硬化临床并发症(如心脏病及中风)中的作用。 然而,弗吉尼亚州夏洛茨维尔大学Gary Owens领导的研究小组目前从小鼠中得到的数据,对这项
据2011年12月27日《医学快线》报道,动脉粥样硬化是重要的动脉血管疾病,它是导致心脏病和中风的主要原因之一。
促炎性分子IL-1与动脉粥样硬化有关,目前已启动了一项临床试验,在该项临床试验中,一种针对IL-1β的特异性抗体被用于研究它在严重的动脉粥样硬化临床并发症(如心脏病及中风)中的作用。
然而,弗吉尼亚州夏洛茨维尔大学Gary Owens领导的研究小组目前从小鼠中得到的数据,对这项临床试验产生了担忧--Owens和他的同事们发现,IL-1限制了进展期动脉粥样硬化中的一些特性,这些特性与人类疾病中严重的并发症相关。
更多信息详见:IL-1信号的失活增加了动脉粥样硬化斑块的不稳定性,同时也降低了小鼠进展期动脉粥样硬化中血管外部的重塑性。(生物谷bioon.com)
Genetic inactivation of IL-1 signaling enhances atherosclerotic plaque instability and reduces outward vessel remodeling in advanced atherosclerosis in mice
Matthew R. Alexander, Christopher W. Moehle, Jason L. Johnson, Zhengyu Yang, Jae K. Lee, Christopher L. Jackson, Gary K. Owens
Clinical complications of atherosclerosis arise primarily as a result of luminal obstruction due to atherosclerotic plaque growth, with inadequate outward vessel remodeling and plaque destabilization leading to rupture. IL-1 is a proinflammatory cytokine that promotes atherogenesis in animal models, but its role in plaque destabilization and outward vessel remodeling is unclear. The studies presented herein show that advanced atherosclerotic plaques in mice lacking both IL-1 receptor type I and apolipoprotein E (Il1r1–/–Apoe–/– mice) unexpectedly exhibited multiple features of plaque instability as compared with those of Il1r1+/+Apoe–/– mice. These features included reduced plaque SMC content and coverage, reduced plaque collagen content, and increased intraplaque hemorrhage. In addition, the brachiocephalic arteries of Il1r1–/–Apoe–/– mice exhibited no difference in plaque size, but reduced vessel area and lumen size relative to controls, demonstrating a reduction in outward vessel remodeling. Interestingly, expression of MMP3 was dramatically reduced within the plaque and vessel wall of Il1r1–/–Apoe–/– mice, and Mmp3–/–Apoe–/– mice showed defective outward vessel remodeling compared with controls. In addition, MMP3 was required for IL-1–induced SMC invasion of Matrigel in vitro. Taken together, these results show that IL-1 signaling plays a surprising dual protective role in advanced atherosclerosis by promoting outward vessel remodeling and enhancing features of plaque stability, at least in part through MMP3-dependent mechanisms.
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