ArticleArteriosclerosis, thrombosis, and vascular biology2004
Inhibition of Rho-kinase leads to rapid activation of phosphatidylinositol 3-kinase/protein kinase Akt and cardiovascular protection.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 1 of them a synthesis that pooled it.
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Who cites it
138 citing papers in PubMed, 1 synthesis or guideline pooled it, 323 citations in OpenAlex.
- Pooled it
- Effects and mechanism of moderate aerobic exercise on impaired fasting glucose improvement.Lipids in health and disease · 2015Trial
- Exogenous nitric oxide inhibits Rho-associated kinase activity in patients with angina pectoris: a randomized controlled trial.Hypertension research : official journal of the Japanese Society of Hypertension · 2015Trial
- Comparison of effects of rosuvastatin (10 mg) versus atorvastatin (40 mg) on rho kinase activity in caucasian men with a previous atherosclerotic event.The American journal of cardiology · 2009 · on this mapTrial
- Rho kinase inhibition improves endothelial function in human subjects with coronary artery disease.Circulation research · 2006Trial
- Review
- Effect of combined aspirin and statin therapy on mortality reduction in sepsis-induced myocardial injury.Frontiers in pharmacology · 2026Article
- Huanglian Jiedu Decoction Alleviates Myocardial Ischemia-Reperfusion Injury via AKT-Mediated Regulation of Endoplasmic Reticulum Stress.Journal of inflammation research · 2025Article
- Untangling the role of RhoA in the heart: protective effect and mechanism.Cell death & disease · 2024Review
- Article
- Pressure Clamping During Ocular Perfusions Drives Nitric Oxide-Mediated Washout.Investigative ophthalmology & visual science · 2023Article
- Paradoxical effects of statins on endothelial and cancer cells: the impact of concentrations.Cancer cell international · 2023Review
- Treatment of cardiac fibrosis: from neuro-hormonal inhibitors to CAR-T cell therapy.Heart failure reviews · 2023Review
- Statins change the cytokine profile inFrontiers in immunology · 2022Article
- Role of EphA4 in Mediating Motor Neuron Death in MND.International journal of molecular sciences · 2021Review
- Role of Rho in Salt-Sensitive Hypertension.International journal of molecular sciences · 2021Review
- Smoking and the Pathophysiology of Peripheral Artery Disease.Frontiers in cardiovascular medicine · 2021Review
- Beneficial Effect of Statin Therapy on Arterial Stiffness.BioMed research international · 2021Review
- Regulator of G-Protein Signaling 5 Maintains Brain Endothelial Cell Function in Focal Cerebral Ischemia.Journal of the American Heart Association · 2020Article
- Activated ROCK/Akt/eNOS and ET-1/ERK pathways in 5-fluorouracil-induced cardiotoxicity: modulation by simvastatin.Scientific reports · 2020Article
78 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
objectiveRho-kinase activity is increased in cardiovascular diseases and in patients with cardiovascular risk factors. However, it is not known whether inhibition of Rho-kinase could lead to cardiovascular protection and, if so, by what mechanism. METHODS AND
resultsIn human endothelial cells, the Rho-kinase inhibitor, hydroxyfasudil (HF) (1 to 100 micromol/L), increased Akt serine-473 phosphorylation within 15 minutes, leading to a 2.2-fold and 4.0-fold increase in Akt kinase activity and nitric oxide (NO) release, respectively. Activation of Akt and eNOS by HF was completely blocked by the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, LY294002 (10 micromol/L). To determine the physiological relevance of this pathway, we used 2 models of ischemia-reperfusion (I/R) injury. Acute administration of fasudil (10 mg/kg, intraperitoneal, 1 hour before ischemia) decreased leukocyte recruitment and adhesion to the mesenteric endothelium after I/R injury in wild-type but not eNOS-/- mice. Similarly, treatment with fasudil decreased myocardial infarct size by 38% in rats subjected to transient coronary artery occlusion. Cotreatment with 2 PI3-kinase inhibitors, wortmannin and LY294002, or the eNOS inhibitor, L-NAME, blocked the cardiovascular protective effects of fasudil.
conclusionsInhibition of Rho-kinase leads to the activation of the PI3-kinase/Akt/eNOS pathway and cardiovascular protection. These findings suggest that Rho-kinase may play an important role in mediating the inflammatory response to I/R injury.
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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.