ArticleCirculation research2012
PPARγ regulates resistance vessel tone through a mechanism involving RGS5-mediated control of protein kinase C and BKCa channel activity.
Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 57 citations in OpenAlex.
- Peroxisome proliferator-activated receptor gamma (PPARγ) as a mechano-metabolic transducer: coordinating lipid homeostasis through mechanical cues.Molecular biomedicine · 2026Review
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- The 2023 Walter B. Cannon Award Lecture: Mechanisms Regulating Vascular Function and Blood Pressure by the PPARγ-RhoBTB1-CUL3 Pathway.Function (Oxford, England) · 2024Review
- RGS proteins and cardiovascular Angiotensin II Signaling: Novel opportunities for therapeutic targeting.Biochemical pharmacology · 2023Review
- CaInternational journal of molecular sciences · 2023Review
- RGS5-TGFβ-Smad2/3 axis switches pro- to anti-apoptotic signaling in tumor-residing pericytes, assisting tumor growth.Cell death and differentiation · 2021Article
- Role of the Peroxisome Proliferator Activated Receptors in Hypertension.Circulation research · 2021Review
- EP3 (E-Prostanoid 3) Receptor Mediates Impaired Vasodilation in a Mouse Model of Salt-Sensitive Hypertension.Hypertension (Dallas, Tex. : 1979) · 2021Article
- Failure to vasodilate in response to salt loading blunts renal blood flow and causes salt-sensitive hypertension.Cardiovascular research · 2021Article
- Salt-Sensitivity of Blood Pressure and Insulin Resistance.Frontiers in physiology · 2021Review
- Cullin-3: Renal and Vascular Mechanisms Regulating Blood Pressure.Current hypertension reports · 2020Review
- PPARγ and RhoBTB1 in hypertension.Current opinion in nephrology and hypertension · 2020Review
- Deficiency of T-type voltage-gated calcium channels results in attenuated weight gain and improved endothelium-dependent dilatation of resistance vessels induced by a high-fat diet in mice.Journal of physiology and biochemistry · 2020Article
- Regulator of G-protein signaling (RGS) proteins as drug targets: Progress and future potentials.The Journal of biological chemistry · 2019Review
- Pharmacological activation of peroxisome proliferator-activated receptor γ (PPAR-γ) protects against hypoxia-associated fetal growth restriction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Conditional deletion of smooth muscle Cullin-3 causes severe progressive hypertension.JCI insight · 2019Article
- Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.Physiological reviews · 2018Review
- Gene expression profiles of ion channels and receptors in mouse resistance arteries: Effects of cell type, vascular bed, and age.Microcirculation (New York, N.Y. : 1994) · 2018Article
- The large-conductance voltage- and CaThe Journal of physiology · 2018Article
- Angiotensin II Type 1 Receptor Mechanoactivation Involves RGS5 (Regulator of G Protein Signaling 5) in Skeletal Muscle Arteries: Impaired Trafficking of RGS5 in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2017Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
rationaleActivation of peroxisome proliferator-activated receptor-γ (PPARγ) by thiazolidinediones lowers blood pressure, whereas PPARγ mutations cause hypertension. Previous studies suggest these effects may be mediated through the vasculature, but the underlying mechanisms remain unclear.
objectiveTo identify PPARγ mechanisms and transcriptional targets in vascular smooth muscle and their role in regulating resistance artery tone. METHODS AND
resultsWe studied mesenteric artery (MA) from transgenic mice expressing dominant-negative (DN) mutant PPARγ driven by a smooth muscle cell-specific promoter. MA from transgenic mice exhibited a robust increase in myogenic tone. Patch clamp analysis revealed a reduced large conductance Ca(2+)-activated K(+) (BKCa) current in freshly dissociated smooth muscle cell from transgenic MA. Inhibition of protein kinase C corrected both enhanced myogenic constriction and impaired the large conductance Ca(2+)-activated K(+) channel function. Gene expression profiling revealed a marked loss of the regulator of G protein signaling 5 (RGS5) mRNA in transgenic MA, which was accompanied by a substantial increase in angiotensin II-induced constriction in MA. Small interfering RNA targeting RGS5 caused augmented myogenic tone in intact mesenteric arteries and increased activation of protein kinase C in smooth muscle cell cultures. PPARγ and PPARδ each bind to a PPAR response element close to the RGS5 promoter. RGS5 expression in nontransgenic MA was induced after activation of either PPARγ or PPARδ, an effect that was markedly blunted by DN PPARγ.
conclusionsWe conclude that RGS5 in smooth muscle is a PPARγ and PPARδ target, which when activated blunts angiotensin II-mediated activation of protein kinase C, and preserves the large conductance Ca(2+)-activated K(+) channel activity, thus providing tight control of myogenic tone in the microcirculation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.