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

J Mol Cell Cardiol 2008 Mar 8;44(3):539-50. Epub 2007 Dec 8.

University of Washington, Department of Pathology, Seattle, Washington 98109, USA.

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 Galphaq/i agonists increased above normal, while 28-day aorta had attenuated induced contraction via Galphaq/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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yjmcc.2007.11.019DOI Listing
March 2008
2 Reads

Publication Analysis

Top Keywords

thoracic aorta
8
abdominal aorta
8
rgs messages
8
rgs5
8
aorta
7
changes
6
angii-dependent angii-independent
4
regulation involves
4
involves angii-dependent
4
wall mass
4
delayed mass
4
messages delayed
4
mass increases
4
increases implying
4
angii-independent pathways
4
implying wall
4
mass regulation
4
pathways abdominal
4
delayed valsartan
4
valsartan treatment
4

Similar Publications