G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes.
Nat Med
; 11(3): 305-11, 2005 Mar.
Article
de En
| MEDLINE
| ID: mdl-15723072
ABSTRACT
Granulocyte colony-stimulating factor (G-CSF) was reported to induce myocardial regeneration by promoting mobilization of bone marrow stem cells to the injured heart after myocardial infarction, but the precise mechanisms of the beneficial effects of G-CSF are not fully understood. Here we show that G-CSF acts directly on cardiomyocytes and promotes their survival after myocardial infarction. G-CSF receptor was expressed on cardiomyocytes and G-CSF activated the Jak/Stat pathway in cardiomyocytes. The G-CSF treatment did not affect initial infarct size at 3 d but improved cardiac function as early as 1 week after myocardial infarction. Moreover, the beneficial effects of G-CSF on cardiac function were reduced by delayed start of the treatment. G-CSF induced antiapoptotic proteins and inhibited apoptotic death of cardiomyocytes in the infarcted hearts. G-CSF also reduced apoptosis of endothelial cells and increased vascularization in the infarcted hearts, further protecting against ischemic injury. All these effects of G-CSF on infarcted hearts were abolished by overexpression of a dominant-negative mutant Stat3 protein in cardiomyocytes. These results suggest that G-CSF promotes survival of cardiac myocytes and prevents left ventricular remodeling after myocardial infarction through the functional communication between cardiomyocytes and noncardiomyocytes.
Recherche sur Google
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Facteur de stimulation des colonies de granulocytes
/
Remodelage ventriculaire
/
Myocytes cardiaques
/
Infarctus du myocarde
Limites:
Animals
Langue:
En
Journal:
Nat Med
Sujet du journal:
BIOLOGIA MOLECULAR
/
MEDICINA
Année:
2005
Type de document:
Article
Pays d'affiliation:
Japon