Wihuri Research Institute, Helsinki, Finland.
Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Eur J Pharmacol. 2017 Dec 5;816:37-46. doi: 10.1016/j.ejphar.2017.10.013. Epub 2017 Oct 12.
Mast cells are potent actors involved in inflammatory reactions in various tissues, including both in the intimal and the adventitial layers of atherosclerotic arteries. In the arterial intima, the site of atherogenesis, mast cells are activated to degranulate, and thereby triggered to release an abundance of preformed inflammatory mediators, notably histamine, heparin, neutral proteases and cytokines stored in their cytoplasmic secretory granules. Depending on the stimulus, mast cell activation may also launch prolonged synthesis and secretion of single bioactive molecules, such as cytokines and derivatives of arachidonic acid. The mast cell-derived mediators may impede the functions of different types of cells present in atherosclerotic lesions, and also compromise the structural and functional integrity of the intimal extracellular matrix. In the adventitial layer of atherosclerotic coronary arteries, mast cells locate next to peptidergic sensory nerve fibers, which, by releasing neuropeptides may activate mast cells to release vasoactive compounds capable of triggering local vasoconstriction. The concerted actions of arterial mast cells have the potential to contribute to the initiation and progression of atherosclerosis, and ultimately to destabilization and rupture of an advanced atherosclerotic plaque with ensuing atherothrombotic complications.
肥大细胞是参与各种组织炎症反应的强效细胞，包括动脉粥样硬化动脉的内膜和外膜层。在内膜，即动脉粥样发生的部位，肥大细胞被激活脱颗粒，从而触发大量预先形成的炎症介质释放，特别是储存在其细胞质分泌颗粒中的组织胺、肝素、中性蛋白酶和细胞因子。根据刺激物的不同，肥大细胞的激活也可能启动单一生物活性分子的长期合成和分泌，如细胞因子和花生四烯酸衍生物。肥大细胞衍生的介质可能会干扰动脉粥样硬化病变中不同类型细胞的功能，还会损害内膜细胞外基质的结构和功能完整性。在动脉粥样硬化性冠状动脉的外膜层，肥大细胞位于肽能感觉神经纤维旁边，这些神经纤维通过释放神经肽可以激活肥大细胞释放血管活性化合物，从而引发局部血管收缩。动脉肥大细胞的协同作用有可能促进动脉粥样硬化的发生和发展，并最终导致晚期动脉粥样硬化斑块的不稳定和破裂，进而引发动脉血栓并发症。
