ArticleThe Journal of clinical investigation2019
RhoBTB1 protects against hypertension and arterial stiffness by restraining phosphodiesterase 5 activity.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 40 citations in OpenAlex.
- Regulation of PDE5 expression in human aorta and thoracic aortic aneurysms.Scientific reports · 2019Trial
- Crosstalk between ubiquitination and other post-translational modifications in cardiovascular diseases.iScience · 2026Review
- Evidence that S-phase kinase associated protein 2 (SKP2) is ubiquitinated and degraded via a Rho-related BTB domain containing 1 (RhoBTB1) and Cullin-3 mechanism in placenta.Physiological reports · 2026Article
- Vascular smooth muscle RbFox2 regulates the cytoskeleton and arterial stiffness by a RhoBTB1/Cullin-3 mechanism.JCI insight · 2026Article
- Transgenerational inheritance of diminished ovarian reserve triggered by prenatal propylparaben exposure in mice.Nature communications · 2025Article
- Cullin-3 regulates the renal baroreceptor machinery that controls renin gene expression.JCI insight · 2025Article
- The effects of space radiation on the transcriptome of heart right ventricle tissue.NPJ microgravity · 2025Article
- Role of the Renin-Angiotensin System in Blood Pressure Regulation in Smooth Muscle-Specific Cullin-3 Deficient Mice.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Familial Hyperkalemic Hypertension.Comprehensive Physiology · 2024Review
- Role of Phosphodiesterases in Biology and Pathology 2.0.International journal of molecular sciences · 2024Article
- The Pathogenesis and Impact of Arterial Stiffening in Hypertension: The 2023 John H. Laragh Research Award.American journal of hypertension · 2024Article
- The 2023 Walter B. Cannon Award Lecture: Mechanisms Regulating Vascular Function and Blood Pressure by the PPARγ-RhoBTB1-CUL3 Pathway.Function (Oxford, England) · 2024Review
- Sex differences in blood pressure regulation and hypertension: renal, hemodynamic, and hormonal mechanisms.Physiological reviews · 2024Review
- Treatment with Ligilactobacillus murinus lowers blood pressure and intestinal permeability in spontaneously hypertensive rats.Scientific reports · 2023Article
- Cullin 3 and Blood Pressure Regulation: Insights From Familial Hyperkalemic Hypertension.Hypertension (Dallas, Tex. : 1979) · 2023Review
- Structure and Function of RhoBTB1 Required for Substrate Specificity and Cullin-3 Ubiquitination.Function (Oxford, England) · 2023Article
- RhoBTB1 reverses established arterial stiffness in angiotensin II-induced hypertension by promoting actin depolymerization.JCI insight · 2022Article
- Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases.Biomolecules · 2022Review
- Transcription of the Envelope Protein by 1-L Protein-RNA Recognition Code Leads to Genes/Proteins That Are Relevant to the SARS-CoV-2 Life Cycle and Pathogenesis.Current issues in molecular biology · 2022Article
- Comorbidities Caused by a Corrupt Cullin 3: Lessons Learned From Bedside to Bench.Hypertension (Dallas, Tex. : 1979) · 2022Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Mice selectively expressing PPARγ dominant negative mutation in vascular smooth muscle exhibit RhoBTB1-deficiency and hypertension. Our rationale was to employ genetic complementation to uncover the mechanism of action of RhoBTB1 in vascular smooth muscle. Inducible smooth muscle-specific restoration of RhoBTB1 fully corrected the hypertension and arterial stiffness by improving vasodilator function. Notably, the cardiovascular protection occurred despite preservation of increased agonist-mediated contraction and RhoA/Rho kinase activity, suggesting RhoBTB1 selectively controls vasodilation. RhoBTB1 augmented the cGMP response to nitric oxide by restraining the activity of phosphodiesterase 5 (PDE5) by acting as a substrate adaptor delivering PDE5 to the Cullin-3 E3 Ring ubiquitin ligase complex for ubiquitination inhibiting PDE5. Angiotensin-II infusion also caused RhoBTB1-deficiency and hypertension which was prevented by smooth muscle specific RhoBTB1 restoration. We conclude that RhoBTB1 protected from hypertension, vascular smooth muscle dysfunction, and arterial stiffness in at least two models of hypertension.
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Registered trials
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.