期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 44, 期 3, 页码 539-550出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2007.11.019
关键词
regulator of G protein signaling; RGS5; vascular hypertrophy; hypertension; aorta; coarctation; GPCR; artery contraction; vascular remodeling
资金
- NHLBI NIH HHS [R01 HL026405, HL03174, P01 HL003174, R37 HL026405, HL26405] Funding Source: Medline
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 I 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 G alpha q/i agonists increased above normal, while 28-day aorta had attenuated induced contraction via G alpha q/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. (C) 2007 Elsevier Inc. All rights reserved.
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