Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Circ Res. 2010 Jan 8;106(1):89-92. doi: 10.1161/CIRCRESAHA.109.204875. Epub 2009 Nov 19.
Although we and others have recently shown that mast cells play an important role in plaque progression and destabilization, the nature of the actual trigger for (peri)vascular mast cell activation during atherosclerosis is still unresolved.
In this study, we confirm that perivascular mast cell content correlates with the number of nerve fibers in the adventitia of human coronary atherosclerotic plaque specimen. Because peripheral C-type nerve fibers secrete, among others, substance P, a potent mast cell activator, we set out to study effects of adventitial administration of this neuropeptide on mast cell dependent destabilization of carotid artery plaques in apolipoprotein E-deficient (apoE(-/-)) mice.
Substance P treatment significantly enhanced the number and activation status of adventitial mast cells compared to controls and promoted intraplaque hemorrhages. These phenomena could be prevented by coadministration of the neurokinin-1 receptor antagonist spantide I and did not occur in mast cell deficient apoE(-/-) mice, establishing the critical involvement of mast cells in substance P-elicited plaque destabilization.
Our data suggest that neurotransmitters such as substance P are capable of promoting mast cell dependent plaque destabilization and provide a new, direct link between neural factors and vascular inflammation.
尽管我们和其他人最近已经表明，肥大细胞在斑块进展和不稳定中发挥重要作用，但在动脉粥样硬化过程中（peri）血管肥大细胞激活的确切触发因素的性质仍未解决。
在这项研究中，我们证实了血管周围肥大细胞含量与人类冠状动脉粥样硬化斑块标本中外膜神经纤维的数量相关。由于外周 C 型神经纤维分泌，除其他外，一种有效的肥大细胞激活剂 P 物质，我们开始研究这种神经肽在载脂蛋白 E 缺陷（apoE（-/-））小鼠颈动脉斑块中依赖肥大细胞的不稳定性的影响。
与对照组相比，P 物质处理显著增加了外膜肥大细胞的数量和激活状态，并促进了斑块内出血。神经激肽-1 受体拮抗剂 spantide I 的共给药可预防这些现象，并且在缺乏肥大细胞的 apoE（-/-）小鼠中不会发生，这表明肥大细胞在 P 物质引起的斑块不稳定中具有关键作用。
我们的数据表明，神经递质如 P 物质能够促进依赖肥大细胞的斑块不稳定性，并为神经因素与血管炎症之间提供了新的直接联系。
