Abstract
The small GTPase RhoA and its downstream effector, Rho kinase (ROCK), appear to mediate numerous pathophysiological signals, including smooth muscle cell contraction, actin cytoskeleton organization, cell adhesion and motility, proliferation, differentiation and the expression of several genes. Clinical interest in the RhoA/ROCK pathway has increased, due to emerging evidence that this signaling pathway is involved in the pathogenesis of several diseases, including hypertension, coronary vasospasm, stroke, atherosclerosis, heart failure and diabetes; ROCK is considered an important future therapeutic target. Several pharmaceutical companies are already actively engaged in the development of ROCK inhibitors as the next generation of therapeutic agents for these diseases. This review discusses the relationship between diabetes and hyperglycemia-induced RhoA/ROCK activation, highlights recent findings on the roles of ROCK inhibitors from experimental models of diabetes and clinical studies in cardiovascular patients, and elucidates major challenges for developing more selective ROCK inhibitors. Accumulating evidence suggests the potential of ROCK inhibitors as therapeutic agents for diabetes and its complications.
Keywords: RhoA, Rho kinase, inhibitors, diabetes, complications, GTPase, hypertension, coronary vasospasm, stroke, atherosclerosis
Current Pharmaceutical Design
Title:Rho Kinase Inhibitors: Potential Treatments for Diabetes and Diabetic Complications
Volume: 18 Issue: 20
Author(s): Hong Zhou and Yong-jun Li
Affiliation:
Keywords: RhoA, Rho kinase, inhibitors, diabetes, complications, GTPase, hypertension, coronary vasospasm, stroke, atherosclerosis
Abstract: The small GTPase RhoA and its downstream effector, Rho kinase (ROCK), appear to mediate numerous pathophysiological signals, including smooth muscle cell contraction, actin cytoskeleton organization, cell adhesion and motility, proliferation, differentiation and the expression of several genes. Clinical interest in the RhoA/ROCK pathway has increased, due to emerging evidence that this signaling pathway is involved in the pathogenesis of several diseases, including hypertension, coronary vasospasm, stroke, atherosclerosis, heart failure and diabetes; ROCK is considered an important future therapeutic target. Several pharmaceutical companies are already actively engaged in the development of ROCK inhibitors as the next generation of therapeutic agents for these diseases. This review discusses the relationship between diabetes and hyperglycemia-induced RhoA/ROCK activation, highlights recent findings on the roles of ROCK inhibitors from experimental models of diabetes and clinical studies in cardiovascular patients, and elucidates major challenges for developing more selective ROCK inhibitors. Accumulating evidence suggests the potential of ROCK inhibitors as therapeutic agents for diabetes and its complications.
Export Options
About this article
Cite this article as:
Zhou Hong and Li Yong-jun, Rho Kinase Inhibitors: Potential Treatments for Diabetes and Diabetic Complications, Current Pharmaceutical Design 2012; 18 (20) . https://dx.doi.org/10.2174/138161212800672688
DOI https://dx.doi.org/10.2174/138161212800672688 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
![](/images/wayfinder.jpg)
- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Gender Differences in Cancer-associated Venous Thromboembolism
Current Medicinal Chemistry Cell Adhesion Molecules and Cadmium
Current Chemical Biology The Possible Adverse Effects of Intramuscular Botulinum Toxin Injections and their Management
Current Drug Safety Identification of Inflammatory, Metabolic, and Cell Survival Pathways Contributing to Cerebral Small Vessel Disease by Postmortem Gene Expression Microarray
Current Neurovascular Research Insulin Resistance and Endothelial Dysfunction: A Mutual Relationship in Cardiometabolic Risk
Current Pharmaceutical Design Subacute Fluoxetine Reduces Signs of Hippocampal Damage Induced by a Single Convulsant Dose of 4-Aminopyridine in Rats
CNS & Neurological Disorders - Drug Targets Exploring Newer Target Sodium Glucose Transporter 2 for the Treatment of Diabetes Mellitus
Mini-Reviews in Medicinal Chemistry Drug-induced Inhibition and Trafficking Disruption of ion Channels: Pathogenesis of QT Abnormalities and Drug-induced Fatal Arrhythmias
Current Cardiology Reviews Molecular Targets of Diabetic Cardiovascular Complications
Current Drug Targets PPAR-γ Agonists in Polycystic Kidney Disease with Frequent Development of Cardiovascular Disorders
Current Molecular Pharmacology The Molecular Targets of Cannabinoids in the Treatment of Cancer and Inflammation
Current Pharmaceutical Design Effects of Elicitors, Viticultural Factors, and Enological Practices on Resveratrol and Stilbenes in Grapevine and Wine
Mini-Reviews in Medicinal Chemistry An Up-date of Olive Oil Phenols in Inflammation and Cancer: Molecular Mechanisms and Clinical Implications
Current Medicinal Chemistry EBI2, GPR18, and GPR17 – Three Structurally Related but Biologically Distinct 7TM Receptors
Current Topics in Medicinal Chemistry Cytokine and Nitric Oxide Production Following Severe Envenomation
Current Drug Targets - Inflammation & Allergy Novel Findings and Therapeutic Targets on Cardioprotection of Ischemia/ Reperfusion Injury in STEMI
Current Pharmaceutical Design Atrial Fibrillation in Acute St-Elevation Myocardial Infarction: Clinical and Prognostic Features
Current Cardiology Reviews Protein Oxidative Modification in the Aging Organism and the Role of the Ubiquitin Proteasomal System
Current Pharmaceutical Design Mitochondrial Mutations in Atherosclerosis: New Solutions in Research and Possible Clinical Applications
Current Pharmaceutical Design Hypothyroidism and Nephrotic Syndrome: Why, When and How to Treat
Current Vascular Pharmacology