Abstract |
Vascular-derived hydrogen peroxide (H2O2) serves as an important signaling molecule in the cardiovascular system and contributes to vascular homeostasis. H2O2 is a second messenger, transducing the oxidative signal into biological responses through posttranslational protein modification. The balance between oxidant and antioxidant systems regulates intracellular redox status, and their imbalance causes oxidative or reductive stress, leading to cellular damage in cardiovascular systems. Excessive H2O2 deteriorates vascular functions and promotes vascular disease through multiple pathways. The RhoA/ Rho-kinase pathway plays an important role in various fundamental cellular functions, including production of excessive reactive oxygen species, leading to the development of cardiovascular diseases. Rho-kinase (ROCK1 and ROCK2) belongs to the family of serine/threonine kinases and is an important downstream effector of the small GTP-binding protein RhoA. Rho-kinase plays a crucial role in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke, and heart failure. Thus, Rho-kinase inhibitors may be useful for the treatment of cardiovascular diseases in humans. In this review, we will briefly discuss the roles of vascular-derived H2O2 and review the recent progress in the translational research on the therapeutic importance of the Rho-kinase pathway in cardiovascular medicine.
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Authors | Hiroaki Shimokawa, Kimio Satoh |
Journal | Journal of cardiovascular pharmacology
(J Cardiovasc Pharmacol)
Vol. 65
Issue 5
Pg. 412-8
(May 2015)
ISSN: 1533-4023 [Electronic] United States |
PMID | 25162437
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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Chemical References |
- Anti-Inflammatory Agents
- Antioxidants
- Cardiovascular Agents
- Inflammation Mediators
- Protein Kinase Inhibitors
- Hydrogen Peroxide
- rho-Associated Kinases
- Cyclophilin A
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Topics |
- Animals
- Anti-Inflammatory Agents
(therapeutic use)
- Antioxidants
(metabolism, therapeutic use)
- Blood Vessels
(drug effects, metabolism, physiopathology)
- Cardiovascular Agents
(therapeutic use)
- Cardiovascular Diseases
(drug therapy, metabolism, physiopathology)
- Cyclophilin A
(metabolism)
- Humans
- Hydrogen Peroxide
(metabolism)
- Inflammation Mediators
(metabolism)
- Oxidation-Reduction
- Oxidative Stress
- Protein Kinase Inhibitors
(therapeutic use)
- Signal Transduction
(drug effects)
- rho-Associated Kinases
(antagonists & inhibitors, metabolism)
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