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

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

doi:10.1016/j.yjmcc.2007.11.019

Cited by 40 publications

(29 citation statements)

References 42 publications

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“…Desensitization toward angiotensin signaling was also indicated at the molecular level by downregulation of the angiotensin receptor, RGS4, and RGS5 (a regulator of G protein signaling molecules); and changes in Rho signaling and calcium handling, as well as in molecules directly involved in initiation of contraction. These findings corresponded well with the proposed role of RGS4 and RGS5, which interact with the G protein-coupled angiotensin receptor type 1 (34), in receptor desensitization together with RGS2 (35). The downregulation of RGS2 and RGS4 might also account for the impaired response of miR-143/145 vessels to phenylephrine, since G protein-coupled receptor-interacting proteins (GIPs) including RGS2 are important components of the adrenergic receptor signalosome (36).…”

Section: Discussionsupporting

confidence: 82%

Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster

Boettger¹,

Beetz²,

Kostin³

et al. 2009

J. Clin. Invest.

597

654

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VSMCs respond to changes in the local environment by adjusting their phenotype from contractile to synthetic, a phenomenon known as phenotypic modulation or switching. Failure of VSMCs to acquire and maintain the contractile phenotype plays a key role in a number of major human diseases, including arteriosclerosis. Although several regulatory circuits that control differentiation of SMCs have been identified, the decisive mechanisms that govern phenotypic modulation remain unknown. Here, we demonstrate that the mouse miR-143/145 cluster, expression of which is confined to SMCs during development, is required for VSMC acquisition of the contractile phenotype. VSMCs from miR-143/145-deficient mice were locked in the synthetic state, which incapacitated their contractile abilities and favored neointimal lesion development. Unbiased high-throughput, quantitative, mass spectrometry-based proteomics using reference mice labeled with stable isotopes allowed identification of miR-143/145 targets; these included angiotensin-converting enzyme (ACE), which might affect both the synthetic phenotype and contractile functions of VSMCs. Pharmacological inhibition of either ACE or the AT 1 receptor partially reversed vascular dysfunction and normalized gene expression in miR-143/145-deficient mice. We conclude that manipulation of miR-143/145 expression may offer a new approach for influencing vascular repair and attenuating arteriosclerotic pathogenesis.

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Section: Discussionsupporting

confidence: 82%

Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster

Boettger¹,

Beetz²,

Kostin³

et al. 2009

J. Clin. Invest.

597

654

View full text Add to dashboard Cite

show abstract

“…In fact, downregulation of RGS5 was accompanied by both an increase in AngII-induced constriction and enhancement of myogenic tone in mouse mesenteric artery (Ketsawatsomkron et al, 2012). Similarly, RGS5 overexpression induced by PPARb activation in the aorta inhibits contractions via Gqa (Wang et al, 2008;Zarzuelo et al, 2011). Moreover, very recently, RGS5 has been identified as a critical modulator of blood pressure and vascular tone, regulating AngII receptor signaling and downstream pathways (Holobotovskyy et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Vascular and Central Activation of Peroxisome Proliferator-Activated Receptor- Attenuates Angiotensin II-Induced Hypertension: Role of RGS-5

Romero

Jiménez

Toral

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Activation of peroxisome proliferator-activated receptor-b/d (PPARb) lowers blood pressure in genetic and mineralocorticoid-induced hypertension. Regulator of G-protein-coupled receptor signaling 5 (RGS5) protein, which interferes in angiotensin II (AngII) signaling, is a target gene to PPARb. The aim of the present study was to examine whether PPARb activation in resistance arteries and brain tissues prevents the elevated blood pressure in AngII-induced hypertension and evaluate the role of RGS5 in this effect. C57BL/6J male mice were divided into five groups (control mice, PPARb agonist phenyl]-4-methyl-5-thiazolyl]methyl]thio]-2-methylphenoxy]acetic acid (GW0742)-treated mice AngII-infused mice, GW0742-treated AngII-infused mice, and AngII-infused mice treated with GW0742 plus PPARb antagonist 3-[[[2-Methoxy-4-(phenylamino)phenyl]amino]sulfonyl]-2-thiophenecarboxylic acid methyl ester (GSK0660)) and were followed for 3 weeks. GW0742 prevented the increase in both arterial blood pressure and plasma noradrenaline levels and the higher reduction of blood pressure after ganglionic blockade, whereas it reduced the mesenteric arterial remodeling and the hyperresponsiveness to vasoconstrictors (AngII and endothelin-1) in AngIIinfused mice. These effects were accompanied by an inhibition of NADPH oxidase expression and activity in the brain. Gene expression profiling revealed a marked loss of brainstem and vascular RGS5 in AngII-infused mice, which was restored by GW0742. GW0742-induced effects were abolished by GSK0660. Small interfering RNA targeting RGS5 caused augmented contractile response to AngII in resistance mesenteric arteries and blunted the inhibitory effect of GW0742 on this response. In conclusion, GW0742 exerted antihypertensive effects, restoring sympathetic tone and vascular structure and function in AngII-infused mice by PPARb activation in brain and vessels inhibiting AngII signaling as a result of RGS5 upregulation.

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“…Unfortunately, receptor internalization is not readily studied in intact tissue with native, untagged, receptors. Prolonged AT 1 receptor activation does however, affect expression of RGS4 and RGS5 mRNAs (38). These mRNAs were therefore used as readouts for angiotensin II signaling.…”

Section: Discussionmentioning

confidence: 99%

“…Increased production of angiotensin II has been previously associated with biphasic changes in the expression of RGS4 and RGS5 (regulators of a G-protein signaling) (38). Furthermore, reduced expression of RGS4/5 mRNA has previously been suggested to be associated with angiotensin II resistance in miR-143/145 KO vascular smooth muscle (8).…”

Section: Mir-143/145 Deletion Increases Ace Expression In Aorta But Nmentioning

confidence: 99%

Induction of angiotensin-converting enzyme after miR-143/145 deletion is critical for impaired smooth muscle contractility

Dahan

Ekman

Larsson‐Callerfelt

et al. 2014

American Journal of Physiology-Cell Physiology

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

Cited by 40 publications

References 42 publications

Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster

Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster

Vascular and Central Activation of Peroxisome Proliferator-Activated Receptor- Attenuates Angiotensin II-Induced Hypertension: Role of RGS-5

Induction of angiotensin-converting enzyme after miR-143/145 deletion is critical for impaired smooth muscle contractility

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