Trial reportArteriosclerosis, thrombosis, and vascular biology2013
Statins exert the pleiotropic effects through small GTP-binding protein dissociation stimulator upregulation with a resultant Rac1 degradation.
Trial report in Arteriosclerosis, thrombosis, and vascular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 86 citations in OpenAlex.
- Statins Reduce Wall Enhancement at Vessel Wall MRI in Unruptured Vertebrobasilar Dissecting Aneurysms: A Randomized Controlled Trial.Radiology · 2025Trial
- Effects of rosuvastatin treatment and other statins on burn wound healing.World journal of methodology · 2026Review
- Cellular lipids: fundamental host factors for monkeypox virus replication and pathogenesis.Archives of microbiology · 2026Review
- Molecular and Immunomodulatory Mechanisms of Statins in Inflammation and Cancer Therapeutics with Emphasis on the NF-κB, NLRP3 Inflammasome, and Cytokine Regulatory Axes.International journal of molecular sciences · 2025Review
- Protein prenylation in islet β-cell function in health and metabolic stress.Biochemical pharmacology · 2025Review
- Review
- Small GTP-binding protein GDP dissociation stimulator influences cisplatin-induced acute kidney injury via PERK-dependent ER stress.Communications biology · 2024Article
- Use of Statins in Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives.International journal of molecular sciences · 2024Review
- Rosuvastatin accelerates the healing process of partial-thickness burn wounds in rats by reducing TNF-α levels.Archives of medical sciences. Atherosclerotic diseases · 2024Article
- Estradiol-mediated small GTP-binding protein GDP dissociation stimulator induction contributes to sex differences in resilience to ferroptosis in takotsubo syndrome.Redox biology · 2023Article
- Mechanisms of Coronary Artery Spasm.European cardiology · 2023Review
- Wound Healing Efficacy of Rosuvastatin Transethosomal Gel, I Optimal Optimization, Histological and In Vivo Evaluation.Pharmaceutics · 2022Article
- RHO GTPase family in hepatocellular carcinoma.Experimental hematology & oncology · 2022Review
- The pleiotropic benefits of statins include the ability to reduce CD47 and amplify the effect of pro-efferocytic therapies in atherosclerosis.Nature cardiovascular research · 2022Article
- RAC1 Activation as a Potential Therapeutic Option in Metastatic Cutaneous Melanoma.Biomolecules · 2021Review
- Review
- The advantages of drug treatment with statins in patients with SARS-CoV-2 infection.Wiener klinische Wochenschrift · 2021Review
- Leptin activates Akt in oesophageal cancer cells via multiple atorvastatin-sensitive small GTPases.Molecular and cellular biochemistry · 2021Article
- Weighted Gene Co-Expression Network Analysis Reveals Key Genes and Potential Drugs in Abdominal Aortic Aneurysm.Biomedicines · 2021Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveThe pleiotropic effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) independent of cholesterol-lowering effects are thought to be mediated through inhibition of the Rho/Rho-kinase pathway. However, we have previously demonstrated that the pleiotropic effects of regular-dose statins are mediated mainly through inhibition of the Rac1 signaling pathway rather than the Rho/Rho-kinase pathway, although the molecular mechanisms of the selective inhibition of the Rac1 signaling pathway by regular-dose statins remain to be elucidated. In this study, we tested our hypothesis that small GTP-binding protein GDP dissociation stimulator (SmgGDS) plays a crucial role in the molecular mechanisms of the Rac1 signaling pathway inhibition by statins in endothelial cells. APPROACH AND
resultsIn cultured human umbilical venous endothelial cells, statins concentration-dependently increased SmgGDS expression and decreased nuclear Rac1. Statins also enhanced SmgGDS expression in mouse aorta. In control mice, the protective effects of statins against angiotensin II-induced medial thickening of coronary arteries and fibrosis were noted, whereas in SmgGDS-deficient mice, the protective effects of statins were absent. When SmgGDS was knocked down by its small interfering RNA in human umbilical venous endothelial cells, statins were no longer able to induce Rac1 degradation or inhibit angiotensin II-induced production of reactive oxygen species. Finally, in normal healthy volunteers, statins significantly increased SmgGDS expression with a significant negative correlation between SmgGDS expression and oxidative stress markers, whereas no correlation was noted with total or low-density lipoprotein-cholesterol.
conclusionsThese results indicate that statins exert their pleiotropic effects through SmgGDS upregulation with a resultant Rac1 degradation and reduced oxidative stress in animals and humans.
Indexed as
Identifiers
What OpenQuestion holds
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.