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Experimental Biology and Medicine 231:794-801 (2006)
© 2006 Society for Experimental Biology and Medicine

VASCULAR AND HYPERTENSION

Expression and Localization of Human Endothelin-Converting Enzyme-1 Isoforms in Symptomatic Atherosclerotic Disease and Saphenous Vein

Carolyn D. Jackson*,1, Kay Barnes*, Shervanthi Homer-Vanniasinkam{dagger} and Anthony J. Turner*

* School of Biochemistry & Microbiology, University of Leeds, Leeds LS29JT, United Kingdom; and {dagger} Vascular Research Unit, Leeds General Infirmary, Great George Street, Leeds LS13EX, United Kingdom

To whom requests for reprints should be addressed at 1 School of Biochemistry and Microbiology, University of Leeds, Leeds LS29JT, United Kingdom. E-mail: c.d.jackson{at}bmb.leeds.ac.uk

Abstract

Endothelin-converting enzyme (ECE-1) is a critical enzyme in the production of the potent vasoconstrictor peptide endothelin (ET-1). It has previously been shown that the levels of both ET-1 and ECE-1 are raised in atherosclerosis, but the possible relevance of the isoforms of ECE-1 in these changes has not yet been investigated. The aim of this study was to examine the expression of the ECE-1a and ECE-1c isoforms in human atherosclerotic pathologies. Immunohistochemical analysis was carried out on sections from atherosclerotic and non-atherosclerotic vascular tissue using a combination of ECE-1 isoform-specific antibodies, anti–{alpha}-actin antibodies to identify smooth muscle cells (SMC) and anti-CD68 antibodies to identify macrophages. ECE-1 isoform expression was also examined in cultured SMC and in macrophages isolated from human blood. Results indicated differences in isoform expression in athero-sclerotic lesions, with distinct patterns of staining for ECE-1a and ECE-1c. ECE-1c immunoreactivity was seen in macrophages, and also correlated with actin staining. ECE-1a was also localized to macrophages and SMC. Results of this study suggest that these local changes influence the expression patterns of the ECE-1 isoforms within individual cell types. Correlation of these isoform expression patterns with the stage of atherosclerosis could provide novel indicators of disease progression.

Key Words: vasculature • atherosclerosis • endothelins






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