The Neuropeptide Substance P Mediates Adventitial Mast Cell Activation and Induces Intraplaque Hemorrhage in Advanced Atherosclerosis
The Neuropeptide Substance P Mediates Adventitial Mast Cell Activation and Induces Intraplaque Hemorrhage in Advanced Atherosclerosis
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DOI：
10.1161/circresaha.109.204875
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发表时间：
2010-01-08
影响因子：
20.1
通讯作者：
Biessen, Erik A. L.
中科院分区：
文献类型：
--
作者：
Bot, Ilze;de Jager, Saskia C. A.;Biessen, Erik A. L.
理论基础：尽管我们和其他人最近已经证明肥大细胞在斑块的发展和不稳定中扮演着重要的角色，但在动脉粥样硬化过程中(周围)血管肥大细胞激活的实际触发因素的性质仍然不清楚。目的：在这项研究中，我们证实了血管周围肥大细胞的含量与人类冠状动脉粥样硬化斑块标本外膜中神经纤维的数量有关。由于外周C型神经纤维分泌P物质，其中P物质是一种有效的肥大细胞激活剂，我们着手研究外膜给予这种神经肽对载脂蛋白E缺陷(apoE(-/-))小鼠颈动脉斑块肥大细胞依赖性失稳的影响。方法和结果：与对照组相比，P物质处理显著增加外膜肥大细胞的数量和激活状态，并促进斑块内出血。神经激肽-1受体拮抗剂Spantide I可以预防这些现象，但在肥大细胞缺陷apoE(-/-)小鼠中没有发生，证实肥大细胞参与了P物质诱导的斑块失稳。结论：我们的数据表明，P物质等神经递质能够促进肥大细胞依赖的斑块失稳，并在神经因素和血管炎症之间提供了一种新的、直接的联系。(中国保监会决议2010；106：89-92。)
Rationale: 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.Objective: 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.Methods and Results: 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.Conclusions: 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. (Circ Res. 2010;106:89-92.)