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(Circulation Research. 2008;103:1359.)
© 2008 American Heart Association, Inc.

Reports

Loss of Bmx Nonreceptor Tyrosine Kinase Prevents Pressure Overload–Induced Cardiac Hypertrophy

Scherise A. Mitchell-Jordan, Tanja Holopainen, Shuxun Ren, Sujing Wang, Sarah Warburton, Michael J. Zhang, Kari Alitalo, Yibin Wang, Thomas M. Vondriska

From the Departments of Anesthesiology (S.A.M.-J., S.R., S. Wang, S. Warburton, M.J.Z., Y.W., T.M.V.), Medicine/Cardiology (Y.W., T.M.V.), and Physiology (Y.W., T.M.V.), David Geffen School of Medicine at the University of California, Los Angeles; and Molecular/Cancer Biology Laboratory (T.H., K.A.), Biomedicum Helsinki, the Haartman Institute and Helsinki University Hospital, University of Helsinki, Finland.

Correspondence to Thomas M. Vondriska, PhD, Departments of Anesthesiology, Medicine & Physiology, BH 557A CHS, 650 Charles Young Dr, UCLA, Los Angeles, CA 90095. E-mail tvondriska{at}mednet.ucla.edu

Abstract

Bmx nonreceptor tyrosine kinase has an established role in endothelial and lymphocyte signaling; however, its role in the heart is unknown. To determine whether Bmx participates in cardiac growth, we subjected mice deficient in the molecule (Bmx knockout mice) to transverse aortic constriction (TAC). In comparison with wild-type mice, which progressively developed massive hypertrophy following TAC, Bmx knockout mice were resistant to TAC-induced cardiac growth at the organ and cell level. Loss of Bmx preserved cardiac ejection fraction and decreased mortality following TAC. These findings are the first to demonstrate a necessary role for the Tec family of tyrosine kinases in the heart and reveal a novel regulator (Bmx) of pressure overload–induced hypertrophic growth.

Key Words: tyrosine kinase • cardiac hypertrophy • signal transduction