Adventitial Mast Cells Connect With Sensory Nerve Fibers in Atherosclerotic Coronary Arteries

Abstract

Background —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. Methods and Results —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. Conclusions —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.