Laine P, Naukkarinen A, Heikkilä L, Penttilä A, Kovanen P T
Wihuri Research Institute, Helsinki, Finland.
Circulation. 2000 Apr 11;101(14):1665-9. doi: 10.1161/01.cir.101.14.1665.
The number of activated mast cells is increased in the adventitia of coronary segments with plaque rupture and in spastic atherosclerotic coronary segments. Neurogenic activation of mast cells has been demonstrated previously in other tissues. Here we identified and quantified contacts between mast cells and nerves in the adventitia of normal and atherosclerotic coronary segments.
Normal (types 0 or I) and atherosclerotic (lesion types II, III, and IV) coronary segments from 22 unselected autopsy cases were stained for mast cells and sensory nerves by a histochemical double-labeling method. Contacts between mast cells and sensory nerves were quantified morphometrically and also identified by confocal microscopy. Coronary arteries obtained during heart transplantation were stained for the neuropeptides capable of stimulating mast cells, ie, substance P and calcitonin gene-related peptide. In the adventitia of atherosclerotic coronary segments with type IV lesions, the numbers of mast cells and mast cell-nerve contacts (104+/-15 mast cells/mm(2) and 30+/-5 nerve contacts/mm(2); mean+/-SEM) were significantly greater than in segments with type III lesions (79+/-12 [P<0.001] and 24+/-6 [P<0.001]), those with type II lesions (54+/-4 [P<0.001] and 12+/-2 [P<0.001]), or those with normal intima (31+/-3 [P<0.001] and 4+/-1 [P<0.001]). The nerve fibers connected with mast cells contained both substance P and calcitonin gene-related peptide, which identified them as sensory nerves.
Neurogenic stimulation of mast cells in the adventitia of coronary arteries may release vasoactive compounds, such as histamine and leukotrienes, which can contribute to the complex neurohormonal response that leads to abnormal coronary vasoconstriction.
在伴有斑块破裂的冠状动脉节段外膜以及痉挛性动脉粥样硬化冠状动脉节段中，活化肥大细胞的数量增加。肥大细胞的神经源性激活先前已在其他组织中得到证实。在此，我们鉴定并量化了正常和动脉粥样硬化冠状动脉节段外膜中肥大细胞与神经之间的接触。
采用组织化学双重标记法，对22例未经选择的尸检病例的正常（0型或I型）和动脉粥样硬化（病变II型、III型和IV型）冠状动脉节段进行肥大细胞和感觉神经染色。通过形态计量学对肥大细胞与感觉神经之间的接触进行量化，并通过共聚焦显微镜进行鉴定。对心脏移植过程中获取的冠状动脉进行能刺激肥大细胞的神经肽染色，即P物质和降钙素基因相关肽。在伴有IV型病变的动脉粥样硬化冠状动脉节段外膜中，肥大细胞数量和肥大细胞 - 神经接触数量（分别为104±15个肥大细胞/mm²和30±5个神经接触/mm²；均值±标准误）显著多于伴有III型病变的节段（分别为79±12个[P<0.001]和24±6个[P<0.001]）、伴有II型病变的节段（分别为54±4个[P<0.001]和12±2个[P<0.001]）或内膜正常的节段（分别为31±3个[P<0.001]和4±1个[P<0.001]）。与肥大细胞相连的神经纤维同时含有P物质和降钙素基因相关肽，这表明它们是感觉神经。
冠状动脉外膜中肥大细胞的神经源性刺激可能释放血管活性化合物，如组胺和白三烯，这可能促成导致冠状动脉异常血管收缩的复杂神经激素反应。
