Trial reportCardiovascular diabetology2012
ROCK inhibitor fasudil attenuated high glucose-induced MCP-1 and VCAM-1 expression and monocyte-endothelial cell adhesion.
Trial report in Cardiovascular diabetology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 60 citations in OpenAlex.
- Fasudil improves short-term echocardiographic parameters of diastolic function in patients with type 2 diabetes with preserved left ventricular ejection fraction: a pilot study.Heart and vessels · 2015Trial
- Gene regulatory network analysis identifies auranofin as an anti-atherosclerotic drug.Nature communications · 2026Article
- Effects of Ripasudil on Mouse Subconjunctival Immune Cell Motility Activated by Monocyte Chemoattractant Protein-1.Investigative ophthalmology & visual science · 2026Article
- Research progress on the mechanisms of interleukin and chemokine families in driving calcium oxalate nephrolithiasis formation.Frontiers in immunology · 2025Review
- Heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation.Diabetologia · 2024Article
- Bromocriptine-QR Therapy Reduces Sympathetic Tone and Ameliorates a Pro-Oxidative/Pro-Inflammatory Phenotype in Peripheral Blood Mononuclear Cells and Plasma of Type 2 Diabetes Subjects.International journal of molecular sciences · 2022Article
- Aquaporin-8 overexpression is involved in vascular structure and function changes in placentas of gestational diabetes mellitus patients.Open life sciences · 2022Article
- HO‑1 knockdown upregulates the expression of VCAM‑1 to induce neutrophil recruitment during renal ischemia‑reperfusion injury.International journal of molecular medicine · 2021Article
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
- Research Progress on Gestational Diabetes Mellitus and Endothelial Dysfunction Markers.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Review
- KRIT1 Deficiency Promotes Aortic Endothelial Dysfunction.International journal of molecular sciences · 2019Article
- Effect of High Glucose on Human Alveolar Macrophage Phenotype and Phagocytosis of Mycobacteria.Lung · 2019Article
- Protection of ripasudil, a Rho kinase inhibitor, in lipopolysaccharides-induced acute pneumonia in mice.American journal of translational research · 2019Article
- Canagliflozin attenuates the progression of atherosclerosis and inflammation process in APOE knockout mice.Cardiovascular diabetology · 2018Article
- Fasudil attenuates soluble fms-like tyrosine kinase-1 (sFlt-1)-induced hypertension in pregnant mice through RhoA/ROCK pathway.Oncotarget · 2017Article
- Fasudil Enhances Therapeutic Efficacy of Neural Stem Cells in the Mouse Model of MPTP-Induced Parkinson's Disease.Molecular neurobiology · 2017Article
- Role of ROCK2 in CD4Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2017Article
- The RhoA/ROCK Pathway Ameliorates Adhesion and Inflammatory Infiltration Induced by AGEs in Glomerular Endothelial Cells.Scientific reports · 2017Article
- Effect of Rho-kinase Inhibitor, Y27632, on Porcine Corneal Endothelial Cell Culture, Inflammation and Immune Regulation.Ocular immunology and inflammation · 2016Article
- A novel inhibitory effect of oxazol-5-one compounds on ROCKII signaling in human coronary artery vascular smooth muscle cells.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrevious studies suggested that the RhoA/ROCK pathway may contribute to vascular complications in diabetes. The present study was designed to investigate whether ROCK inhibitor fasudil could prevent high glucose-induced monocyte-endothelial cells adhesion, and whether this was related to fasudil effects on vascular endothelial cell expression of chemotactic factors, vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1).
methodsHUVECs were stimulated with high glucose (HG) or HG + fasudil in different concentration or different time. Monocyte-endothelial cell adhesion was determined using fluorescence-labeled monocytes. The mRNA and protein expression of VCAM-1 and MCP-1 were measured using real-time PCR and western blot. The protein levels of RhoA, ROCKI and p-MYPT were determined using western blot analysis. ELISA was employed to measure the expression of soluble VCAM-1 and MCP-1 in cell supernatants and human serum samples.
resultsFasudil significantly suppressed HG-induced adhesion of THP-1 to HUVECs. Fasudil reduced Rho/ROCK activity (as indicated by lower p-MYPT/MYPT ratio), and prevented HG induced increases in VCAM-1 and MCP-1 mRNA and protein levels. Fasudil also decreased MCP-1 concentration in HUVEC supernatants, but increased sVCAM-1 shedding into the media. In human diabetic subjects, 2 weeks of fasudil treatment significantly decreased serum MCP-1 level from 27.9 ± 10.6 pg/ml to 13.8 ± 7.0 pg/ml (P < 0.05), while sVCAM-1 increased from 23.2 ± 7.5 ng/ml to 39.7 ± 5.6 ng/ml after fasudil treatment (P < 0.05).
conclusionsTreatment with the Rho/ROCK pathway inhibitor fasudil attenuated HG-induced monocyte-endothelial cell adhesion, possibly by reducing endothelial expression of VCAM-1 and MCP-1. These results suggest inhibition of Rho/ROCK signaling may have therapeutic potential in preventing diabetes associated vascular inflammation and atherogenesis.
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