Adventitial mast cells connect with sensory nerve fibers in atherosclerotic coronary arteries

Background-The number of activated mast cells is increased in the adventiti a of coronary segments with plaque rupture and in spastic atherosclerotic c oronary segments. Neurogenic activation of mast cells has been demonstrated previously in other tissues. Here we identified and quantified contacts be tween mast cells and nerves in the adventitia of normal and atherosclerotic coronary segments. Methods and Results-Normal (types 0 or I) and atherosclerotic (lesion types II, III, and IV) coronary segments from 22 unselected autopsy cases were s tained for mast cells and sensory nerves by a histochemical double-labeling method. Contacts between mast cells and sensory nerves were quantified mor phometrically and also identified by confocal microscopy, Coronary arteries obtained during heart transplantation were stained for the neuropeptides c apable of stimulating mast cells, ie, substance P and calcitonin gene-relat ed peptide. In the adventitia of atherosclerotic coronary segments with typ e 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 sign ificantly 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 substan ce P and calcitonin gene-related peptide, which identified them as sensory nerves. Conclusions-Neurogenic stimulation of mast cells in the adventitia of coron ary arteries may release vasoactive compounds, such as histamine and leukot rienes, which can contribute to the complex neurohormonal response that lea ds to abnormal coronary vasoconstriction.