Bot Ilze, de Jager Saskia C A, Zernecke Alma, Lindstedt Ken A, van Berkel Theo J C, Weber Christian, Biessen Erik A L
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, PO Box 9502, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Circulation. 2007 May 15;115(19):2516-25. doi: 10.1161/CIRCULATIONAHA.106.660472. Epub 2007 Apr 30.
Mast cells are major effector cells in allergy and host defense responses. Their increased number and state of activation in perivascular tissue during atherosclerosis may point to a role in cardiovascular disorders. In the present study, we investigated the contribution of perivascular mast cells to atherogenesis and plaque stability in apolipoprotein E-deficient mice.
We show here that episodes of systemic mast cell activation during plaque progression in mice leads to robust plaque expansion. Targeted activation of perivascular mast cells in advanced plaques sharply increases the incidence of intraplaque hemorrhage, macrophage apoptosis, vascular leakage, and CXCR2/VLA-4-mediated recruitment of leukocytes to the plaque. Importantly, treatment with the mast cell stabilizer cromolyn does prevent all the adverse phenomena elicited by mast cell activation.
This is the first study to demonstrate that mast cells play a crucial role in plaque progression and destabilization in vivo. We propose that mast cell stabilization could be a new therapeutic approach to the prevention of acute coronary syndromes.
肥大细胞是过敏和宿主防御反应中的主要效应细胞。在动脉粥样硬化过程中，其在血管周围组织中的数量增加和激活状态可能表明其在心血管疾病中发挥作用。在本研究中，我们调查了血管周围肥大细胞对载脂蛋白E缺陷小鼠动脉粥样硬化形成和斑块稳定性的影响。
我们在此表明，小鼠斑块进展过程中全身性肥大细胞激活事件会导致斑块显著扩张。晚期斑块中血管周围肥大细胞的靶向激活会急剧增加斑块内出血、巨噬细胞凋亡、血管渗漏以及CXCR2/VLA-4介导的白细胞向斑块募集的发生率。重要的是，用肥大细胞稳定剂色甘酸钠治疗确实可以预防肥大细胞激活引发的所有不良现象。
这是第一项证明肥大细胞在体内斑块进展和不稳定中起关键作用的研究。我们提出，稳定肥大细胞可能是预防急性冠状动脉综合征的一种新的治疗方法。
