Our aim was to compare the cellular expression of endothelin-converting enzyme-1 (ECE-1) isoforms and ECE-2 using immunocytochemistry in normal and diseased human tissue. Intense ECE-1b immunoreactivity was present within renal and pulmonary epithelial cells with lower levels of staining displayed by ECE-1c, ECE-1a and ECE-2 antisera. Staining was detected with all antisera (except ECE-1a) within the endothelium of renal and pulmonary vessels having a range of lumen diameters as well as pial arteries and intracerebral vessels penetrating brain. ECE-1b, ECE-1c and ECE-2 immunoreactivity was localized to perivascular astrocytes and neuronal processes in the cerebral cortex. In diseased vessels, ECE-1c, ECE-1b and ECE-2 antisera stained macrophages infiltrating atherosclerotic plaques within coronary arteries. These results suggest ECE-1b and ECE-2 may be widely expressed in normal tissue from humans and inhibition of ECE-1 isoforms and ECE-2 expressed by cells such as macrophages in pathophysiological tissue may be an additional therapeutic target in cardiovascular disease.
Address correspondence and reprint requests to Dr A.P. Davenport, Clinical Pharmacology Unit, Box 110, University of Cambridge, Level 6, Centre for Clinical Investigation, Addenbrookes Hospital, Cambridge, CB2 2QQ, U.K. E-mail: [email protected]; http://www-davenport.medsch1.cam.ac.uk/
© 2000 Lippincott Williams & Wilkins, Inc.