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Central role of Gq in the hypertrophic signal transduction of angiotensin II in vascular smooth muscle cells.

Authors
  • Ohtsu, Haruhiko
  • Higuchi, Sadaharu
  • Shirai, Heigoro
  • Eguchi, Kunie
  • Suzuki, Hiroyuki
  • Hinoki, Akinari
  • Brailoiu, Eugen
  • Eckhart, Andrea D
  • Frank, Gerald D
  • Eguchi, Satoru
Type
Published Article
Journal
Endocrinology
Publication Date
Jul 01, 2008
Volume
149
Issue
7
Pages
3569–3575
Identifiers
DOI: 10.1210/en.2007-1694
PMID: 18356277
Source
Medline
License
Unknown

Abstract

The angiotensin II (AngII) type 1 receptor (AT(1)) plays a critical role in hypertrophy of vascular smooth muscle cells (VSMCs). Although it is well known that G(q) is the major G protein activated by the AT(1) receptor, the requirement of G(q) for AngII-induced VSMC hypertrophy remains unclear. By using cultured VSMCs, this study examined the requirement of G(q) for the epidermal growth factor receptor (EGFR) pathway, the Rho-kinase (ROCK) pathway, and subsequent hypertrophy. AngII-induced intracellular Ca(2+) elevation was completely inhibited by a pharmacological G(q) inhibitor as well as by adenovirus encoding a G(q) inhibitory minigene. AngII (100nm)-induced EGFR transactivation was almost completely inhibited by these inhibitors, whereas these inhibitors only partially inhibited AngII (100nm)-induced phosphorylation of a ROCK substrate, myosin phosphatase target subunit-1. Stimulation of VSMCs with AngII resulted in an increase of cellular protein and cell volume but not in cell number. The G(q) inhibitors completely blocked these hypertrophic responses, whereas a G protein-independent AT(1) agonist did not stimulate these hypertrophic responses. In conclusion, G(q) appears to play a major role in the EGFR pathway, leading to vascular hypertrophy induced by AngII. Vascular G(q) seems to be a critical target of intervention against cardiovascular diseases associated with the enhanced renin-angiotensin system.

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