Nadph Oxidase Modulates Myocardial Akt, Erk1/2 Activation, and Angiogenesis After Hypoxia-reoxygenation.
From: Department of Pediatrics, Division of Neonatology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2650, USA. jian-xiong.chen@vanderbilt.edu
American journal of physiology. Heart and circulatory physiology
- Publish Date: Apr 2007
- ISSN: 0363-6135
- Volume: 292
- Issue: 4
- Pages: H1664-74
- Medium: Print
- Language: English
- Citation (JAMA): Chen Jian-Xiong, Zeng Heng, Tuo Qin-Hui, et al. Nadph Oxidase Modulates Myocardial Akt, Erk1/2 Activation, and Angiogenesis After Hypoxia-reoxygenation.. Am. J. Physiol. Heart Circ. Physiol. Apr 2007;292:H1664-74
Abstract
Recent studies have demonstrated that reactive oxygen species (ROS) mediate myocardial ischemia-reperfusion (I/R) and angiogenesis via the mitogen-activated protein kinases and the serine-threonine kinase Akt/protein kinase B pathways. NADPH oxidases are major sources of ROS in endothelial cells and cardiomyocytes. In the present study, we investigated the role of NADPH oxidase-derived ROS in hypoxia-reoxygenation (H/R)-induced Akt and ERK1/2 activation and angiogenesis using porcine coronary artery endothelial cells (PCAECs) and a mouse myocardial I/R model. Our data demonstrate that exposure of PCAECs to hypoxia for 2 h followed by 1 h of reoxygenation significantly increased ROS formation. Pretreatment with the NADPH oxidase inhibitors, diphenyleneiodonium (DPI, 10 microM) and apocynin (Apo, 200 and 600 microM), significantly attenuated H/R-induced ROS formation. Furthermore, exposure of PCAECs to H/R caused a significant increase in Akt and ERK1/2 activation. Exposure of PCAEC spheroids and mouse aortic rings to H/R significantly increased endothelial spheroid sprouting and vessel outgrowth, whereas pharmacological inhibition of NADPH oxidase or genetic deletion of the NADPH oxidase subunit, p47(phox) (p47(phox-/-)), significantly suppressed these changes. With the use of a mouse I/R model, our data further show that the increases in myocardial Akt and ERK1/2 activation and vascular endothelial growth factor (VEGF) expression were markedly blunted in the p47(phox-/-) mouse subjected to myocardial I/R compared with the wild-type mouse. Our findings underscore the important role of NADPH oxidase and its subunit p47(phox) in modulating Akt and ERK1/2 activation, angiogenic growth factor expression, and angiogenesis in myocardium undergoing I/R.
Mesh Headings (Keywords): Animals, Anoxia, Cells, Cultured, Collagen, Coronary Vessels, Endothelial Cells, Gels, MAP Kinase Signaling System, Mice, Mice, Knockout, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Myocardial Ischemia, Myocardial Reperfusion Injury, NADPH Oxidase, Neovascularization, Physiologic, Proto-Oncogene Proteins c-akt, Reactive Oxygen Species, Spheroids, Cellular, Superoxides, Swine
Check for Full Text / PubMed Unique Identifier (PMID): 17220182
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.