Abstract-Locally formed angiotensin II (Ang II) and mast cells may participate in the development of atherosclerosis.Chymase, which originates from mast cells, is the major Ang II-forming enzyme in the human heart and aorta in vitro.The aim of the present study was to investigate aortic Ang II-forming activity (AIIFA) and the histochemical localization of each Ang II-forming enzyme in the atheromatous human aorta. Specimens of normal (nϭ9), atherosclerotic (nϭ8), and aneurysmal (nϭ6) human aortas were obtained at autopsy or cardiovascular surgery from 23 subjects (16 men, 7 women). The total, angiotensin-converting enzyme (ACE)-dependent, and chymase-dependent AIIFAs in aortic specimens were determined. The histologic and cellular localization of chymase and ACE were determined by immunocytochemistry. Total AIIFA was significantly higher in atherosclerotic and aneurysmal lesions than in normal aortas. Most of AIIFA in the human aorta in vitro was chymase-dependent in both normal (82%) and atherosclerotic aortas (90%). Immunocytochemical staining of the corresponding aortic sections with antichymase, antitryptase or anti-ACE antibodies showed that chymase-positive mast cells were located in the tunica adventitia of normal and atheromatous aortas, whereas ACE-positive cells were localized in endothelial cells of normal aorta and in macrophages of atheromatous neointima. The density of chymase-and tryptase-positive mast cells in the atherosclerotic lesions was slightly but not significantly higher than that in the normal aortas, and the number of activated mast cells in the aneurysmal lesions (18%) was significantly higher than in atherosclerotic (5%) and normal (1%) aortas. Our results suggest that local Ang II formation is increased in atherosclerotic lesions and that chymase is primarily responsible for this increase. The histologic localization and potential roles of chymase in the development of atherosclerotic lesions appear to be different from those of ACE. (Hypertension. 1999;33:1399-1405.)

The aims of this study were to compare human cardiac angiotensin-II-forming activity (AIIFA) between the intact area of control autopsy hearts without cardiac disease (n = 10) and the infarcted or non-infarcted area of autopsy hearts with myocardial infarction (MI, n = 7) and to determine responsible angiotensin-II-forming enzymes. Cardiac total and chymase-dependent AIIFAs were significantly higher in the infarcted and non-infarcted myocardium than those in non-MI heart, while angiotensin-converting enzyme-dependent AIIFA increased only in the infarcted myocardium. The density of chymase antibody-positive mast cells in the non-infarcted area of MI heart correlated positively with total or chymase-dependent AIIFA. Augmented AIIFA was also detected in the left atrium of post-MI hearts. Our results indicated that cardiac angiotensin II formation could be activated in the infarcted as well as in non-infarcted myocardium of the post-MI human heart.

Abstract. The role of mast cells (MC) in tubulointerstitial damage in glomerulonephritis (GN) is not fully understood. The distribution of MC was compared in renal biopsies from 50 patients with different stages of rapidly progressive GN (RPGN) and in 20 control samples. The immunoreactivity of renal MC with anti-tryptase and anti-chymase antibodies was studied. Interstitial myofibroblasts were stained with anti-α-smooth muscle actin (α-SMA) antibody, and inflammatory cells were identified by anti-CD3, -CD20, and -CD68 monoclonal antibodies. Positively stained cells were counted, and the relative interstitial and fractional areas of anti-α-SMA-stained cells were measured. MC were rarely found in control samples. In contrast, samples showing crescentic GN contained numerous tryptase-positive MC (MCT) (43.7 ± 4.65 versus 7.14 ± 1.3/mm2) and fewer tryptase- and chymase-positive MC (MCTC) (13.8 ± 1.86 versus 1.89 ± 0.86/mm2) in the renal interstitium but never in the glomerulus. Double immunostaining demonstrated the presence of both phenotypes of MC. Accumulation of MC was significantly correlated with the numbers of T lymphocytes (MCT, r = 0.67) and interstitial macrophages (MCT, r = 0.455). There was also a significant correlation between the number of MCT and the relative interstitial area. The number of MCTC was well correlated with the fractional area of α-SMA-positive interstitium (r = 0.749) and the percentage of the interstitial fibrotic area (r = 0.598). There was also a significant negative correlation between interstitial MCTC accumulation and creatinine clearance (r = 0.661). The density of MCTC was higher (1.4-fold) in advanced forms of GN associated with fibrocellular crescents and interstitial fibrosis. These results show the potential involvement of MC in the fibroproliferative process in the renal interstitium of patients with RPGN. The results indicate that these cells constitute part of the overall inflammatory cell accumulation in RPGN.

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