AngII (angiotensin II) and its G-protein-coupled AT1 receptor play critical roles in mediating cardiovascular diseases such as hypertension, atherosclerosis and restenosis after vascular injury. It is widely believed that AngII promotes these diseases by inducing vascular remodelling that involves hypertrophy, hyperplasia and migration of VSMCs (vascular smooth muscle cells). We have shown that transactivation of an ErbB family receptor, EGFR (epidermal growth factor receptor; ErbB1), is essential for VSMC hypertrophy and migration induced by AngII. However, the precise signal transduction mechanism by which AngII transactivates EGFR/ErbB1 and whether other ErbBs are also required for AngII function remains unclear. Recent studies suggest an involvement of a metalloprotease-dependent ErbB family ligand production in the transactivation. Here, we will discuss the roles and mechanisms of AngII/AT1 receptor in promoting ErbB receptors transactivation in VSMCs. Further elucidation of this ErbB activation machinery not only will give us a better understanding of the critical molecular mechanism underlying vascular remodelling stimulated by AngII, but will also contribute to development of novel treatment strategies for cardiovascular diseases.
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December 2003
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Conference Article|
December 01 2003
Metalloprotease-dependent ErbB ligand shedding in mediating EGFR transactivation and vascular remodelling
S. Eguchi;
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, U.S.A.
2To whom correspondence should be addressed (e-mail seguchi@temple.edu).
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G.D. Frank;
G.D. Frank
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, U.S.A.
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M. Mifune;
M. Mifune
1
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, U.S.A.
2To whom correspondence should be addressed (e-mail seguchi@temple.edu).
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T. Inagami
T. Inagami
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, U.S.A.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2003 Biochemical Society
2003
Biochem Soc Trans (2003) 31 (6): 1198–1202.
Citation
S. Eguchi, G.D. Frank, M. Mifune, T. Inagami; Metalloprotease-dependent ErbB ligand shedding in mediating EGFR transactivation and vascular remodelling. Biochem Soc Trans 1 December 2003; 31 (6): 1198–1202. doi: https://doi.org/10.1042/bst0311198
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