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(Hypertension. 2006;47:339.)
© 2006 American Heart Association, Inc.

Editorial Commentaries

Growth Factor Receptor Transactivation in Mediating End Organ Damage by Angiotensin II

From the Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, Philadelphia, Pa.

Correspondence to Satoru Eguchi, MD, PhD, FAHA, Cardiovascular Research Center, Temple University School of Medicine, 3420 N. Broad St, Philadelphia, PA 19140. E-mail seguchi@temple.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Angiotensin II (Ang II) and its major heterotrimeric G protein-coupled receptor (GPCR) AT₁ have long been believed to mediate end organ damage associated with cardiovascular and metabolic diseases. In the past decade, efforts have been made to dissect intracellular signal transduction mechanisms by which Ang II exerts its pathophysiological effects on target cells and tissues. Recent accumulating evidence suggests the critical role of the "transactivation" of the growth factor receptors with intrinsic tyrosine kinase activity in this context. Transactivation of the platelet-derived growth factor receptor (PDGFR) and epidermal growth factor receptor (EGFR) could be mediated by numbers of GPCRs, including the AT₁ receptor that ap-pears to activate important downstream signal transductions and functions such as extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (ERK/MAPK), cell growth, and migration.¹ However, there is still a void in our knowledge regarding the relative contribution of PDGFR and EGFR in end organ damage together with cardiovascular remodeling induced by Ang II as well as detailed molecular mechanisms by which AT₁ mediates the growth factor receptor transactivation.

The article by Schellings et al in this issue of Hypertension² provides significant insights into the pathophysiological roles of the growth factor receptor transactivation in hypertensive end organ damage induced by Ang II. The study demonstrates that despite continuous hypertension and left ventricular hypertrophy, the cardiac dysfunction induced in the transgenic Ren2 rat (a model of Ang II-driven hypertension and end organ damage) was attenuated by a tyrosine kinase inhibitor, imatinib mesy-late, which preferentially blocks the PDGFR. The tissue protective . . . [Full Text of this Article]