ArticleJournal of the American Heart Association2018
Rac1 Modulates Endothelial Function and Platelet Aggregation in Diabetes Mellitus.
Article in Journal of the American Heart Association, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Defective efferocytosis in diabetes: molecular mechanisms and emerging therapeutic strategies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Serum RAC1 as a potential biomarker in the early stages of diabetic kidney disease.Diabetology & metabolic syndrome · 2025Article
- Clearing Amyloid-Beta by Astrocytes: The Role of Rho GTPases Signaling Pathways as Potential Therapeutic Targets.Brain sciences · 2024Review
- Mechanisms of endothelial activation, hypercoagulation and thrombosis in COVID-19: a link with diabetes mellitus.Cardiovascular diabetology · 2024Review
- C2CD4B Evokes Oxidative Stress and Vascular Dysfunction via a PI3K/Akt/PKCα-Signaling Pathway.Antioxidants (Basel, Switzerland) · 2024Article
- Association of nitric oxide levels and lipid profile with endothelial dysfunction in type 2 diabetic patients.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2024Article
- Design, Synthesis,Journal of medicinal chemistry · 2023Article
- Targeting the ASMase/S1P pathway protects from sortilin-evoked vascular damage in hypertension.The Journal of clinical investigation · 2022Article
- The Etiology and Molecular Mechanism Underlying Smooth Muscle Phenotype Switching in Intimal Hyperplasia of Vein Graft and the Regulatory Role of microRNAs.Frontiers in cardiovascular medicine · 2022Review
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
- Regulation of Rac1 transcription by histone and DNA methylation in diabetic retinopathy.Scientific reports · 2021Article
- Inhibition of miR-155 Attenuates Detrimental Vascular Effects of Tobacco Cigarette Smoking.Journal of the American Heart Association · 2020Article
- GPCRs, G Proteins, and Their Impact on β-cell Function.Comprehensive Physiology · 2020Review
- PERK-Mediated Unfolded Protein Response Activation and Oxidative Stress in PARK20 Fibroblasts.Frontiers in neuroscience · 2019Article
- The Main Determinants of Diabetes Mellitus Vascular Complications: Endothelial Dysfunction and Platelet Hyperaggregation.International journal of molecular sciences · 2018Review
- Review
- Risk factors and a model for prognosis prediction after intravenous thrombolysis with alteplase in acute ischemic stroke based on propensity score matching.International journal of immunopathology and pharmacologyArticle
- Effect of admission serum glucose on the clinical prognosis of patients with acute ischemic stroke receiving alteplase intravenous thrombolysis.International journal of immunopathology and pharmacologyArticle
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVascular complications and abnormal platelet function contribute to morbidity and mortality in diabetes mellitus. We hypothesized that the Rho-related GTPase protein, Rac1, can influence both endothelial and platelet function and might represent a potential novel therapeutic target in diabetes mellitus. METHODS AND
resultsWe used both in vitro and ex vivo approaches to test the effects of pharmacological inhibition of Rac1 during hyperglycemic condition. We evaluated the effect of NSC23766, a pharmacological inhibitor of Rac1, on vascular function in diabetic mice and platelet aggregation in diabetic subjects. We demonstrated that the administration of NSC23766 protects from hyperglycemia-induced endothelial dysfunction, restoring NO levels, and reduces oxidative stress generated by nicotinamide adenine dinucleotide phosphate oxidase. Mechanistically, we identified Rho-associated coiled-coil serine/threonine kinase-1 as a downstream target of Rac1. Moreover, we reported that during hyperglycemic conditions, human platelets showed hyperactivation of Rac1 and impaired NO release, which were both partially restored after NSC23766 treatment. Finally, we characterized the antiplatelet effect of NSC23766 during hyperglycemic conditions, demonstrating the additional role of Rac1 inhibition in reducing platelet aggregation in diabetic patients treated with common antiplatelet drugs.
conclusionsOur data suggest that the pharmacological inhibition of Rac1 could represent a novel therapeutic strategy to reduce endothelial dysfunction and platelet hyperaggregation in diabetes mellitus.
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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.