RGS5, RGS4, and RGS2 expression and aortic contractibility are dynamically co-regulated during aortic banding-induced hypertrophy

Wang, Xi; Adams, Lawrence D.; Pabón, Lil M.; Mahoney, William M.; Beaudry, Diane; Gunaje, Jagadambika; Geary, Randolph L.; deBlois, Denis; Schwartz, Stephen M.

doi:10.1016/j.yjmcc.2007.11.019

« Previous Next »Journal of Molecular and Cellular Cardiology
Volume 44, Issue 3 , Pages 539-550, March 2008

RGS5, RGS4, and RGS2 expression and aortic contractibility are dynamically co-regulated during aortic banding-induced hypertrophy

Xi Wang
- University of Washington, Department of Pathology, Seattle, Washington 98109, USA
- Co-first authors.
Lawrence D. Adams
- University of Washington, Department of Pathology, Seattle, Washington 98109, USA
- Corresponding author. Department of Pathology, 815 Mercer Street, Rm. 419, Seattle, WA 98109-4714. Tel.: +1 206 543 7483; fax: +1 206 897 1540.
- Co-first authors.
Lil M. Pabón
- University of Washington, Department of Pathology, Seattle, Washington 98109, USA
William M. Mahoney Jr.
- University of Washington, Department of Pathology, Seattle, Washington 98109, USA
Diane Beaudry
- University of Montreal, Montreal, Quebec, Canada H2W 1T8
Jagadambika Gunaje
- University of Washington, Department of Pathology, Seattle, Washington 98109, USA
Randolph L. Geary
- Wake Forest University, Winston-Salem, North Carolina 27157, USA
Denis deBlois
- University of Montreal, Montreal, Quebec, Canada H2W 1T8
Stephen M. Schwartz
- University of Washington, Department of Pathology, Seattle, Washington 98109, USA

Received 16 July 2007; received in revised form 4 October 2007; accepted 29 November 2007.

Abstract

Overexpression of regulator of G protein signaling 5 (RGS5) in arteries over veins is the most striking difference observed using microarray analysis. The obvious question is what arterial function might require RGS5. Based on functions of homologous proteins in regulating cardiac mass and G-protein-coupled receptor (GPCR) signaling, we proposed that RGS5 and vascular expressed RGS2 and RGS4 could participate in regulating arterial hypertrophy. We used the suprarenal abdominal aorta banding model to induce hypertension and hypertrophy. All 3 RGS messages were expressed in unmanipulated aorta with RGS5 predominating. After 2 days, thoracic aorta lost expression of RGS5, 4, and 2. At 1 week, all three returned to normal, and at 28 days, they increased many fold above normal. Valsartan blockade of angiotensin II (angII)/angII type 1 receptor signaling prevented upregulation of RGS messages but only delayed mass increases, implying wall mass regulation involves both angII-dependent and angII-independent pathways. The abdominal aorta showed less dramatic expression changes in RGS5 and 4, but not 2. Again, those changes were delayed by valsartan treatment with no mass changes. Thoracic aorta contraction to GPCR agonists was examined in aortic explant rings to identify vessel wall physiological changes. In 2-day aorta, the response to Gαq/i agonists increased above normal, while 28-day aorta had attenuated induced contraction via Gαq/i agonist, implicating a connection between RGS message levels and changes in GPCR-induced contraction. In vitro overexpression studies showed RGS5 inhibits angII-induced signaling in smooth muscle cells. This study is the first experimental evidence that changes in RGS expression and function correlate with vascular remodeling.

Keywords: Regulator of G protein signaling, RGS5, Vascular hypertrophy, Hypertension, Aorta, Coarctation, GPCR, Artery contraction, Vascular remodeling