Activation of vascular p38MAPK by mechanical stretch is independent of c-Src and NADPH oxidase: influence of hypertension and angiotensin II |
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| Authors: | Tamara M. Paravicini Augusto C. Montezano Hiba Yusuf Rhian M. Touyz |
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| Affiliation: | 1. Kidney Research Centre, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada;2. School of Biomedical Sciences, The University of Queensland, Brisbane, Australia;3. Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK;3. Nephrology Section, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030;4. Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas 77030;5. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030;6. Department of Surgery, Baylor College of Medicine, Houston, Texas 77030;3. IRCCS-Policlinico San Donato, 20097 Milan, Italy;4. Istituto Dermopatico dell''Immacolata-IRCCS, 00167 Rome, Italy;5. Istituto Nazionale dei Tumori Regina Elena, 00158 Rome, Italy;6. Uniklinikum-Goethe University, 60590 Frankfurt am Main, Germany;3. Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University Vienna, A-1030 Vienna, Austria;4. Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University SE-S-10691 Stockholm, Sweden;1. Department of Physiology, Tsurumi University School of Dental Medicine, Yokohama 230-8501, Japan;2. Department of Orthodontics, Tsurumi University School of Dental Medicine, Yokohama 230-8501, Japan;3. Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan;1. Department of Vascular and Endovascular Surgery, Technische Universität, Munich, Germany;2. Mechanics & High Performance Computing Group, Technische Universität, Munich, Germany;3. Institute for Computational Mechanics, Technische Universität, Munich, Germany |
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| Abstract: | ![]()
Little is known about vascular MAPK regulation in response to mechanical strain. Whether mechanically-sensitive pathways are altered in hypertension is unclear. We examined effects of stretch and Ang II on activation of p38MAPK in vascular smooth muscle cells (VSMC) from WKY and SHR. The role of c-Src and redox-sensitive pathways in stretch-induced effects were examined. VSMC from mesenteric arteries were plated onto flexible silastic plates and exposed to acute or chronic cyclic stretch (10%, 1 Hz) with or without Ang II (0.1 uM). Acute stretch stimulated p38MAPK activation in WKY and SHR, independently of c-Src and reactive oxygen species (ROS), since PP2 (c-Src inhibitor) and apocynin (NADPH oxidase inhibitor), failed to alter stretch-mediated p38MAPK. Chronic stretch blunted p38MAPK phosphorylation in WKY and increased phosphorylation in SHR. Stretch, in the presence of Ang II, induced an increase in procollagen-1 expression. This was blocked by SB203580 (p38MAPK inhibitor). Accordingly, vascular p38MAPK is a mechano-sensitive MAPK, differentially regulated by acute and chronic stretch in WKY and SHR. Functionally, stretch and Ang II, amplify profibrotic responses in a p38MAPK-dependent manner, responses that are perturbed in SHR. Such molecular process may influence vascular fibrosis in hypertension and appear to be independent of c-Src and ROS. |
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