ArticleJCI insight2019
Conditional deletion of smooth muscle Cullin-3 causes severe progressive hypertension.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 30 citations in OpenAlex.
- A Selective Cullin 3 RING E3 Ligase Inhibitor Attenuates Hyperglycemia via Dual Insulin Sensitizing and Insulinotropic Action.Diabetes · 2026Article
- 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
- Arterial stiffness and vascular aging: mechanisms, prevention, and therapy.Signal transduction and targeted therapy · 2025Review
- Cullin-3 regulates the renal baroreceptor machinery that controls renin gene expression.JCI insight · 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
- 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
- Insights into the diverse mechanisms and effects of variant CUL3-induced familial hyperkalemic hypertension.Cell communication and signaling : CCS · 2023Review
- Cullin 3 and Blood Pressure Regulation: Insights From Familial Hyperkalemic Hypertension.Hypertension (Dallas, Tex. : 1979) · 2023Review
- Obesity-related vascular dysfunction persists after weight loss and is associated with decreased vascular glucagon-like peptide receptor in female rats.American journal of physiology. Heart and circulatory physiology · 2022Article
- Restoration of Cullin3 gene expression enhances the improved effects of sonic hedgehog signaling activation for hypertension and attenuates the dysfunction of vascular smooth muscle cells.Biomedical engineering online · 2022Article
- Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases.Biomolecules · 2022Review
- CUL3 and COPS5 Related to the Ubiquitin-Proteasome Pathway Are Potential Genes for Muscle Atrophy in Mice.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Comorbidities Caused by a Corrupt Cullin 3: Lessons Learned From Bedside to Bench.Hypertension (Dallas, Tex. : 1979) · 2022Article
- Endothelial Cullin3 Mutation Impairs Nitric Oxide-Mediated Vasodilation and Promotes Salt-Induced Hypertension.Function (Oxford, England) · 2022Article
- Article
- Role of the central renin‑angiotensin system in hypertension (Review).International journal of molecular medicine · 2021Review
- Role of the Peroxisome Proliferator Activated Receptors in Hypertension.Circulation research · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Patients with mutations in Cullin-3 (CUL3) exhibit severe early onset hypertension but the contribution of the smooth muscle remains unclear. Conditional genetic ablation of CUL3 in vascular smooth muscle (S-CUL3KO) causes progressive impairment in responsiveness to nitric oxide (NO), rapid development of severe hypertension, and increased arterial stiffness. Loss of CUL3 in primary aortic smooth muscle cells or aorta resulted in decreased expression of the NO receptor, soluble guanylate cyclase (sGC), causing a marked reduction in cGMP production and impaired vasodilation to cGMP analogues. Vasodilation responses to a selective large conductance Ca2+-activated K+-channel activator were normal suggesting that downstream signals which promote smooth muscle-dependent relaxation remained intact. We conclude that smooth muscle specific CUL3 ablation impairs both cGMP production and cGMP responses and that loss of CUL3 function selectively in smooth muscle is sufficient to cause severe hypertension by interfering with the NO-sGC-cGMP pathway. Our study provides compelling evidence for the sufficiency of vascular smooth muscle CUL3 as a major regulator of BP. CUL3 mutations cause severe vascular dysfunction, arterial stiffness and hypertension due to defects in vascular smooth muscle.
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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.