GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:12388077

From GONUTS
Jump to: navigation, search
Citation

Cohen, AW, Park, DS, Woodman, SE, Williams, TM, Chandra, M, Shirani, J, Pereira de Souza, A, Kitsis, RN, Russell, RG, Weiss, LM, Tang, B, Jelicks, LA, Factor, SM, Shtutin, V, Tanowitz, HB and Lisanti, MP (2003) Caveolin-1 null mice develop cardiac hypertrophy with hyperactivation of p42/44 MAP kinase in cardiac fibroblasts. Am. J. Physiol., Cell Physiol. 284:C457-74

Abstract

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.

Links

PubMed Online version:10.1152/ajpcell.00380.2002

Keywords

Animals; Atrial Natriuretic Factor/genetics; Cardiomegaly/enzymology; Cardiomegaly/genetics; Cardiomegaly/pathology; Caveolae/metabolism; Caveolae/pathology; Caveolin 1; Caveolins/deficiency; Caveolins/genetics; Cell Membrane/genetics; Cell Membrane/metabolism; Cell Membrane/pathology; Extracellular Matrix/genetics; Extracellular Matrix/metabolism; Extracellular Matrix/pathology; Female; Fibroblasts/enzymology; Fibroblasts/pathology; Hypertrophy, Left Ventricular/genetics; Hypertrophy, Left Ventricular/metabolism; Hypertrophy, Left Ventricular/pathology; Immunohistochemistry; Magnetic Resonance Imaging; Male; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases/metabolism; Myocardium/enzymology; Myocardium/pathology; Myocytes, Cardiac/enzymology; Myocytes, Cardiac/pathology; Ventricular Dysfunction, Right/genetics; Ventricular Dysfunction, Right/metabolism; Ventricular Dysfunction, Right/pathology

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

See Help:References for how to manage references in GONUTS.