Regulator of G protein signaling 5 marks peripheral arterial smooth muscle cells and is downregulated in atherosclerotic plaque

Abstract

These data identify RGS5 as a new member of a short list of genes uniquely expressed in peripheral arteries but not coronary arteries. Persistence of an arterial pattern of RGS5 expression in culture and lack of expression in coronary arteries support a unique SMC phenotype fixed by distinct lineage or differentiation pathways. The association between loss of expression and arterial wall disease has prompted the new hypothesis that prolonged inhibition by RGS5 of vasoactive or trophic G protein signaling is critical to normal peripheral artery function.

PPARδ-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis

“…Both RGS4 and RGS5 have been reported to be negative regulators of AngII signaling through the AT1 receptor (32,33), suggesting that AngII can enhance its own signaling by down-regulating RGS4 and RGS5. Barish et al have shown that PPAR␦ ligands increase RGS4 and RGS5 expression in the aorta (7,34). Similarly, we found that GW0742 prevented the AngII-induced down-regulation of RGS4 and RGS5 in the aorta and inhibited AngII activation of macrophage p38 and ERK1/2 MAP kinases, as well as downstream c-fos activation (data not shown).…”

Coexpression of Notch3 and Rgs5 in the pericyte-vascular smooth muscle cell axis in response to pulp injury

“…Pericytes may change their phenotype along the pericyte-vSMC axis (Nehls and Drenckhahn, 1993;Andreeva et al, 1998). Previous reports have suggested RGS5 as a marker for pericytes Cho et al, 2003), vSMCs (Li et al, 2004) and activated pericytes during wound healing and vascular remodeling (Berger et al, 2005). The present results show that Rgs5 and Notch3 are co-expressed in the pericytes and along the vSMC axis.…”

“…The present results show that Rgs5 and Notch3 are co-expressed in the pericytes and along the vSMC axis. RGS proteins are regulators of the G-protein and have been implicated in the control of chondroblast (Appleton et al, 2006) and osteoblast (Thirunavukkarasu et al, 2002) differentiation, as well as in the differentiation of mural cells during embryonic vascular maturation and peripheral artery function (Li et al, 2004). Notch3 is crucial for tissue homeostasis since mutation of this gene leads to CADASIL, a systemic disease in the arterioles (Brulin et al, 2002).…”

Regulator of G-Protein Signaling 5 Prevents Smooth Muscle Cell Proliferation and Attenuates Neointima Formation

“…8 Initially, RGS5 was found to be specifically expressed in the SMCs of the aorta and peripheral arteries and in pericytes. 9,10 More recent studies in mice lacking RGS5 expression have shown that a loss of RGS5 leads to hypertension, vessel hypertrophy, and vascular stiffening and correlates with hyper-responsiveness to angiotensin II, endothelin-1, norepinephrine, and thrombin, suggesting that RGS5 plays a pivotal role in attenuating the effects of the aforementioned vasoconstrictors. 6 Inasmuch as these vasoconstrictors also drive SMC growth, RGS5 may also function as an inhibitor of chronic trophic signals within the artery wall.…”