Immunohistochemical localization of Betacellulin, a member of epidermal growth factor family, in atherosclerotic plaques of human aorta

Betacellulin (BTC), a new member of the EGF family. has been reported to be a potent mitogen for rat vascular smooth muscle cells (SMCs). ETC mRNA is known to be expressed in several human organs. However. the localization of ETC in human vascular tissues has not yet been clarified. We investigated whether or not ETC protein is involved in the pathogenesis of human atherosclerosis. Recombinant human ETC showed a mitogenic activity on cultured human aortic SMCs by measuring [H-3]thymidine incorporation. The immunohistochemical localization of BTC. SMCs, macrophages, EGF receptors and ErbB4 was examined in autopsied human aortas. ETC was detected in both intimal and medial SMCs of the aortic wall. The percentage of ETC-positive medial SMCs in early types of atherosclerotic lesions decreased with age, but in adult, it was significantly higher in advanced types than in early types of atherosclerotic lesions. ETC-positive SMCs were predominantly localized in the medial side of the intima. Furthermore, numerous ETC-positive SMCs and macrophages were observed around the core lesion of atherosclerotic plaques. Receptors. fur ETC. EGF receptor and ErbB4, were expressed on SMCs, suggesting that ETC is associated with EGF receptor family-mediated signaling. ETC is produced in human aortic tissue and might play important roles in atherogenesis. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.