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Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy
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| Zeitschriftentitel: | Journal of Experimental Medicine |
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| Personen und Körperschaften: | , , , , , , , , , , , , , , , , |
| In: | Journal of Experimental Medicine, 206, 2009, 8, S. 1787-1802 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Rockefeller University Press
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| Schlagwörter: |
| author_facet |
Pilichou, Kalliopi Remme, Carol Ann Basso, Cristina Campian, Maria E. Rizzo, Stefania Barnett, Phil Scicluna, Brendon P. Bauce, Barbara van den Hoff, Maurice J.B. de Bakker, Jacques M.T. Tan, Hanno L. Valente, Marialuisa Nava, Andrea Wilde, Arthur A.M. Moorman, Antoon F.M. Thiene, Gaetano Bezzina, Connie R. Pilichou, Kalliopi Remme, Carol Ann Basso, Cristina Campian, Maria E. Rizzo, Stefania Barnett, Phil Scicluna, Brendon P. Bauce, Barbara van den Hoff, Maurice J.B. de Bakker, Jacques M.T. Tan, Hanno L. Valente, Marialuisa Nava, Andrea Wilde, Arthur A.M. Moorman, Antoon F.M. Thiene, Gaetano Bezzina, Connie R. |
|---|---|
| author |
Pilichou, Kalliopi Remme, Carol Ann Basso, Cristina Campian, Maria E. Rizzo, Stefania Barnett, Phil Scicluna, Brendon P. Bauce, Barbara van den Hoff, Maurice J.B. de Bakker, Jacques M.T. Tan, Hanno L. Valente, Marialuisa Nava, Andrea Wilde, Arthur A.M. Moorman, Antoon F.M. Thiene, Gaetano Bezzina, Connie R. |
| spellingShingle |
Pilichou, Kalliopi Remme, Carol Ann Basso, Cristina Campian, Maria E. Rizzo, Stefania Barnett, Phil Scicluna, Brendon P. Bauce, Barbara van den Hoff, Maurice J.B. de Bakker, Jacques M.T. Tan, Hanno L. Valente, Marialuisa Nava, Andrea Wilde, Arthur A.M. Moorman, Antoon F.M. Thiene, Gaetano Bezzina, Connie R. Journal of Experimental Medicine Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy Immunology Immunology and Allergy |
| author_sort |
pilichou, kalliopi |
| spelling |
Pilichou, Kalliopi Remme, Carol Ann Basso, Cristina Campian, Maria E. Rizzo, Stefania Barnett, Phil Scicluna, Brendon P. Bauce, Barbara van den Hoff, Maurice J.B. de Bakker, Jacques M.T. Tan, Hanno L. Valente, Marialuisa Nava, Andrea Wilde, Arthur A.M. Moorman, Antoon F.M. Thiene, Gaetano Bezzina, Connie R. 1540-9538 0022-1007 Rockefeller University Press Immunology Immunology and Allergy http://dx.doi.org/10.1084/jem.20090641 <jats:p>Mutations in the cardiac desmosomal protein desmoglein-2 (DSG2) are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC). We studied the explanted heart of a proband carrying the DSG2-N266S mutation as well as transgenic mice (Tg-NS) with cardiac overexpression of the mouse equivalent of this mutation, N271S-dsg2, with the aim of investigating the pathophysiological mechanisms involved. Transgenic mice recapitulated the clinical features of ARVC, including sudden death at young age, spontaneous ventricular arrhythmias, cardiac dysfunction, and biventricular dilatation and aneurysms. Investigation of transgenic lines with different levels of transgene expression attested to a dose-dependent dominant-negative effect of the mutation. We demonstrate for the first time that myocyte necrosis is the key initiator of myocardial injury, triggering progressive myocardial damage, including an inflammatory response and massive calcification within the myocardium, followed by injury repair with fibrous tissue replacement, and myocardial atrophy. These observations were supported by findings in the explanted heart from the patient. Insight into mechanisms initiating myocardial damage in ARVC is a prerequisite to the future development of new therapies aimed at delaying onset or progression of the disease.</jats:p> Myocyte necrosis underlies progressive myocardial dystrophy in mouse <i>dsg2</i>-related arrhythmogenic right ventricular cardiomyopathy Journal of Experimental Medicine |
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| title |
Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy |
| title_unstemmed |
Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy |
| title_full |
Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy |
| title_fullStr |
Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy |
| title_full_unstemmed |
Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy |
| title_short |
Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy |
| title_sort |
myocyte necrosis underlies progressive myocardial dystrophy in mouse <i>dsg2</i>-related arrhythmogenic right ventricular cardiomyopathy |
| topic |
Immunology Immunology and Allergy |
| url |
http://dx.doi.org/10.1084/jem.20090641 |
| publishDate |
2009 |
| physical |
1787-1802 |
| description |
<jats:p>Mutations in the cardiac desmosomal protein desmoglein-2 (DSG2) are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC). We studied the explanted heart of a proband carrying the DSG2-N266S mutation as well as transgenic mice (Tg-NS) with cardiac overexpression of the mouse equivalent of this mutation, N271S-dsg2, with the aim of investigating the pathophysiological mechanisms involved. Transgenic mice recapitulated the clinical features of ARVC, including sudden death at young age, spontaneous ventricular arrhythmias, cardiac dysfunction, and biventricular dilatation and aneurysms. Investigation of transgenic lines with different levels of transgene expression attested to a dose-dependent dominant-negative effect of the mutation. We demonstrate for the first time that myocyte necrosis is the key initiator of myocardial injury, triggering progressive myocardial damage, including an inflammatory response and massive calcification within the myocardium, followed by injury repair with fibrous tissue replacement, and myocardial atrophy. These observations were supported by findings in the explanted heart from the patient. Insight into mechanisms initiating myocardial damage in ARVC is a prerequisite to the future development of new therapies aimed at delaying onset or progression of the disease.</jats:p> |
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| author | Pilichou, Kalliopi, Remme, Carol Ann, Basso, Cristina, Campian, Maria E., Rizzo, Stefania, Barnett, Phil, Scicluna, Brendon P., Bauce, Barbara, van den Hoff, Maurice J.B., de Bakker, Jacques M.T., Tan, Hanno L., Valente, Marialuisa, Nava, Andrea, Wilde, Arthur A.M., Moorman, Antoon F.M., Thiene, Gaetano, Bezzina, Connie R. |
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| description | <jats:p>Mutations in the cardiac desmosomal protein desmoglein-2 (DSG2) are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC). We studied the explanted heart of a proband carrying the DSG2-N266S mutation as well as transgenic mice (Tg-NS) with cardiac overexpression of the mouse equivalent of this mutation, N271S-dsg2, with the aim of investigating the pathophysiological mechanisms involved. Transgenic mice recapitulated the clinical features of ARVC, including sudden death at young age, spontaneous ventricular arrhythmias, cardiac dysfunction, and biventricular dilatation and aneurysms. Investigation of transgenic lines with different levels of transgene expression attested to a dose-dependent dominant-negative effect of the mutation. We demonstrate for the first time that myocyte necrosis is the key initiator of myocardial injury, triggering progressive myocardial damage, including an inflammatory response and massive calcification within the myocardium, followed by injury repair with fibrous tissue replacement, and myocardial atrophy. These observations were supported by findings in the explanted heart from the patient. Insight into mechanisms initiating myocardial damage in ARVC is a prerequisite to the future development of new therapies aimed at delaying onset or progression of the disease.</jats:p> |
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| spelling | Pilichou, Kalliopi Remme, Carol Ann Basso, Cristina Campian, Maria E. Rizzo, Stefania Barnett, Phil Scicluna, Brendon P. Bauce, Barbara van den Hoff, Maurice J.B. de Bakker, Jacques M.T. Tan, Hanno L. Valente, Marialuisa Nava, Andrea Wilde, Arthur A.M. Moorman, Antoon F.M. Thiene, Gaetano Bezzina, Connie R. 1540-9538 0022-1007 Rockefeller University Press Immunology Immunology and Allergy http://dx.doi.org/10.1084/jem.20090641 <jats:p>Mutations in the cardiac desmosomal protein desmoglein-2 (DSG2) are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC). We studied the explanted heart of a proband carrying the DSG2-N266S mutation as well as transgenic mice (Tg-NS) with cardiac overexpression of the mouse equivalent of this mutation, N271S-dsg2, with the aim of investigating the pathophysiological mechanisms involved. Transgenic mice recapitulated the clinical features of ARVC, including sudden death at young age, spontaneous ventricular arrhythmias, cardiac dysfunction, and biventricular dilatation and aneurysms. Investigation of transgenic lines with different levels of transgene expression attested to a dose-dependent dominant-negative effect of the mutation. We demonstrate for the first time that myocyte necrosis is the key initiator of myocardial injury, triggering progressive myocardial damage, including an inflammatory response and massive calcification within the myocardium, followed by injury repair with fibrous tissue replacement, and myocardial atrophy. These observations were supported by findings in the explanted heart from the patient. Insight into mechanisms initiating myocardial damage in ARVC is a prerequisite to the future development of new therapies aimed at delaying onset or progression of the disease.</jats:p> Myocyte necrosis underlies progressive myocardial dystrophy in mouse <i>dsg2</i>-related arrhythmogenic right ventricular cardiomyopathy Journal of Experimental Medicine |
| spellingShingle | Pilichou, Kalliopi, Remme, Carol Ann, Basso, Cristina, Campian, Maria E., Rizzo, Stefania, Barnett, Phil, Scicluna, Brendon P., Bauce, Barbara, van den Hoff, Maurice J.B., de Bakker, Jacques M.T., Tan, Hanno L., Valente, Marialuisa, Nava, Andrea, Wilde, Arthur A.M., Moorman, Antoon F.M., Thiene, Gaetano, Bezzina, Connie R., Journal of Experimental Medicine, Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy, Immunology, Immunology and Allergy |
| title | Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy |
| title_full | Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy |
| title_fullStr | Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy |
| title_full_unstemmed | Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy |
| title_short | Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy |
| title_sort | myocyte necrosis underlies progressive myocardial dystrophy in mouse <i>dsg2</i>-related arrhythmogenic right ventricular cardiomyopathy |
| title_unstemmed | Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy |
| topic | Immunology, Immunology and Allergy |
| url | http://dx.doi.org/10.1084/jem.20090641 |