ArticleJournal of the American Heart Association2014
Smooth muscle specific Rac1 deficiency induces hypertension by preventing p116RIP3-dependent RhoA inhibition.
Article in Journal of the American Heart Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Antipsychotic-like effects of the selective Rho-kinase 2 inhibitor KD025 in genetic and pharmacological mouse models of schizophrenia.Molecular psychiatry · 2026Article
- Research Progress on the ARHGEF Family in Cardiovascular Diseases.Cell biochemistry and function · 2026Review
- Vasoactivity of Rac GTPase, Cytohesin and Kinase Inhibitors in Renal Interlobar and Coronary Arteries Reveals Shared and Distinct Patterns of Inhibitory Effects in Vascular and Prostate Smooth Muscle Contraction.Pharmacology research & perspectives · 2025Article
- Review
- RAC1 is involved in uterine myometrium contraction in the inflammation-associated preterm birth.Reproduction (Cambridge, England) · 2022Article
- Smooth muscle Rac1 contributes to pulmonary hypertension.British journal of pharmacology · 2022Article
- New Functions of Vav Family Proteins in Cardiovascular Biology, Skeletal Muscle, and the Nervous System.Biology · 2021Review
- Activation of neuronal Ras-related C3 botulinum toxin substrate 1 (Rac1) improves post-stroke recovery and axonal plasticity in mice.Journal of neurochemistry · 2021Article
- Regulation of smooth muscle contraction by monomeric non-RhoA GTPases.British journal of pharmacology · 2020Review
- Caught between a "Rho" and a hard place: are CCN1/CYR61 and CCN2/CTGF the arbiters of microvascular stiffness?Journal of cell communication and signaling · 2020Review
- Inhibition of Female and Male Human Detrusor Smooth Muscle Contraction by the Rac Inhibitors EHT1864 and NSC23766.Frontiers in pharmacology · 2020Article
- Vascular Smooth Muscle Remodeling in Conductive and Resistance Arteries in Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2018Review
- FSD-C10 Shows Therapeutic Effects in Suppressing oxidized low-density lipoprotein (ox-LDL)-Induced Human Brain Microvascular Endothelial Cells Apoptosis via Rho-Associated Coiled-Coil Kinase (ROCK)/Mitogen-Activated Protein Kinase (MAPK) Signaling.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Sustained Activation of Rho GTPases Promotes a Synthetic Pulmonary Artery Smooth Muscle Cell Phenotype in Neprilysin Null Mice.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Benefit of Mineralocorticoid Receptor Antagonism in AKI: Role of Vascular Smooth Muscle Rac1.Journal of the American Society of Nephrology : JASN · 2017Article
- A Genetic Response Score for Hydrochlorothiazide Use: Insights From Genomics and Metabolomics Integration.Hypertension (Dallas, Tex. : 1979) · 2016Article
- Functional and Proteomic Investigations Reveal Major Royal Jelly Protein 1 Associated with Anti-hypertension Activity in Mouse Vascular Smooth Muscle Cells.Scientific reports · 2016Article
- Article
- Vav family exchange factors: an integrated regulatory and functional view.Small GTPases · 2014Review
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreasing evidence implicates overactivation of RhoA as a critical component of the pathogenesis of hypertension. Although a substantial body of work has established that Rac1 functions antagonize RhoA in a broad range of physiological processes, the role of Rac1 in the regulation of vascular tone and blood pressure is not fully elucidated. METHODS AND
resultsTo define the role of Rac1 in vivo in vascular smooth muscle cells (vSMC), we generated smooth muscle (SM)-specific Rac1 knockout mice (SM-Rac1-KO) and performed radiotelemetric blood pressure recordings, contraction measurements in arterial rings, vSMC cultures and biochemical analyses. SM-Rac1-KO mice develop high systolic blood pressure sensitive to Rho kinase inhibition by fasudil. Arteries from SM-Rac1-KO mice are characterized by a defective NO-dependent vasodilation and an overactivation of RhoA/Rho kinase signaling. We provide evidence that Rac1 deletion-induced hypertension is due to an alteration of cGMP signaling resulting from the loss of Rac1-mediated control of type 5 PDE activity. Consequently, cGMP-dependent phosphorylation and binding of RhoA with its inhibitory partner, the phosphatase-RhoA interacting protein (p116(RIP3)), are decreased.
conclusionsOur data reveal that the depletion of Rac1 in SMC decreases cGMP-dependent p116(RIP3)/RhoA interaction and the subsequent inhibition of RhoA signaling. Thus, we unveil an in vivo role of Rac1 in arterial blood pressure regulation and a new pathway involving p116(RIP3) that contributes to the antagonistic relationship between Rac1 and RhoA in vascular smooth muscle cells and their opposite roles in arterial tone and blood pressure.
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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.