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2014
- doi: 10.1093/eurheartj/ehs269
- issn: 0195-668X
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Contractile fibroblasts Instruction and study--Methods Balance Cardiac cells Cardiomyocytes Cardiocytes Service of process Service of papers Abuse of process Process Populations, Human Human populations Population growth Human population Birth Myocytes Mouse House mice Mus musculus House mouse Birth Obstetric labor Heart enlargement Myocardial hypertrophy Cardiomegaly Heart--Hypertrophy and dilatation Cardiac hypertrophy Heart--Enlargement Enlargement of the heart Hypertrophic cardiomyopathy Cardiac fibrosis Curing (Medicine) Fibrocytes Desmocytes Balancing (Physics) Balance (Physics) Balance Birth Birthing Live birth Child birth Instruction and study--Methods Date of birth Biography--Birth Demography Demographics EnlargementCiter ce document
M. Nemir et al., « The Notch pathway controls fibrotic and regenerative repair in the adult heart. », Serveur académique Lausannois, ID : 10.1093/eurheartj/ehs269
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AIMS: In the adult heart, Notch signalling regulates the response to injury. Notch inhibition leads to increased cardiomyocyte apoptosis, and exacerbates the development of cardiac hypertrophy and fibrosis. The role of Notch in the mesenchymal stromal cell fraction, which contains cardiac fibroblasts and cardiac precursor cells, is, however, largely unknown. In the present study, we evaluate, therefore, whether forced activation of the Notch pathway in mesenchymal stromal cells regulates pathological cardiac remodelling. METHODS AND RESULTS: We generated transgenic mice overexpressing the Notch ligand Jagged1 on the surface of cardiomyocytes to activate Notch signalling in adjacent myocyte and non-myocyte cells. In neonatal transgenic mice, activated Notch sustained cardiac precursor and myocyte proliferation after birth, and led to increased numbers of cardiac myocytes in adult mice. In the adult heart under pressure overload, Notch inhibited the development of cardiomyocyte hypertrophy and transforming growth factor-β/connective tissue growth factor-mediated cardiac fibrosis. Most importantly, Notch activation in the stressed adult heart reduced the proliferation of myofibroblasts and stimulated the expansion of stem cell antigen-1-positive cells, and in particular of Nkx2.5-positive cardiac precursor cells. CONCLUSIONS: We conclude that Notch is pivotal in the healing process of the injured heart. Specifically, Notch regulates key cellular mechanisms in the mesenchymal stromal cell population, and thereby controls the balance between fibrotic and regenerative repair in the adult heart. Altogether, these findings indicate that Notch represents a unique therapeutic target for inducing regeneration in the adult heart via mobilization of cardiac precursor cells.