Caveolin-1 null mice develop cardiac hypertrophy with hyperactivation of p42/44 MAP kinase in cardiac fibroblasts
| Autor: | Michael P. Lisanti, Stephen M. Factor, Jamshid Shirani, Scott Eric Woodman, Richard N. Kitsis, Terrence M. Williams, Robert G. Russell, David S. Park, Linda A. Jelicks, Herbert B. Tanowitz, Louis M. Weiss, Baiyu Tang, Andrea Pereira De Souza, Vitaliy Shtutin, Madhulika Chandra, Alex W. Cohen |
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| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Physiology Ventricular Dysfunction Right Caveolin 1 Cardiomegaly Context (language use) Biology Caveolae Caveolins Muscle hypertrophy Mice Internal medicine medicine Animals Myocytes Cardiac Mice Knockout Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Hyperactivation Myocardium Cell Membrane Null (mathematics) Cell Biology Fibroblasts Immunohistochemistry Magnetic Resonance Imaging Null allele Extracellular Matrix Cell biology Endocrinology Mitogen-activated protein kinase cardiovascular system biology.protein Female Hypertrophy Left Ventricular Mitogen-Activated Protein Kinases Atrial Natriuretic Factor |
| Zdroj: | American Journal of Physiology-Cell Physiology. 284:C457-C474 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00380.2002 |
| Popis: | Recently, development of a caveolin-1-deficient (Cav-1 null) mouse model has allowed the detailed analysis of caveolin-1's function in the context of a whole animal. Interestingly, we now report that the hearts of Cav-1 null mice are markedly abnormal, despite the fact that caveolin-1 is not expressed in cardiac myocytes. However, caveolin-1 is abundantly expressed in the nonmyocytic cells of the heart, i.e., cardiac fibroblasts and endothelia. Quantitative imaging studies of Cav-1 null hearts demonstrate a significantly enlarged right ventricular cavity and a thickened left ventricular wall with decreased systolic function. Histological analysis reveals myocyte hypertrophy with interstitial/perivascular fibrosis. Because caveolin-1 is thought to act as a negative regulator of the p42/44 MAP kinase cascade, we performed Western blot analysis with phospho-specific antibodies that only recognize activated ERK1/2. As predicted, the p42/44 MAP kinase cascade is hyperactivated in Cav-1 null heart tissue (i.e., interstitial fibrotic lesions) and isolated cardiac fibroblasts. In addition, endothelial and inducible nitric oxide synthase levels are dramatically upregulated. Thus loss of caveolin-1 expression drives p42/44 MAP kinase activation and cardiac hypertrophy. |
| Databáze: | OpenAIRE |
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