Autophagy-mediated degradation is necessary for regression of cardiac hypertrophy during ventricular unloading.
Biochem Biophys Res Commun
; 441(4): 787-92, 2013 Nov 29.
Article
em En
| MEDLINE
| ID: mdl-24211573
ABSTRACT
Cardiac hypertrophy occurs in response to a variety of stresses as a compensatory mechanism to maintain cardiac output and normalize wall stress. Prevention or regression of cardiac hypertrophy can be a major therapeutic target. Although regression of cardiac hypertrophy occurs after control of etiological factors, the molecular mechanisms remain to be clarified. In the present study, we investigated the role of autophagy in regression of cardiac hypertrophy. Wild-type mice showed cardiac hypertrophy after continuous infusion of angiotensin II for 14 days using osmotic minipumps, and regression of cardiac hypertrophy was observed 7 days after removal of the minipumps. Autophagy was induced during regression of cardiac hypertrophy, as evidenced by an increase in microtubule-associated protein 1 light chain 3 (LC3)-II protein level. Then, we subjected cardiac-specific Atg5-deficient (CKO) and control mice (CTL) to angiotensin II infusion for 14 days. CKO and CTL developed cardiac hypertrophy to a similar degree without contractile dysfunction. Seven days after removal of the minipumps, CKO showed significantly less regression of cardiac hypertrophy compared with CTL. Regression of pressure overload-induced cardiac hypertrophy after unloading was also attenuated in CKO. These results suggest that autophagy is necessary for regression of cardiac hypertrophy during unloading of neurohumoral and hemodynamic stress.
Palavras-chave
Angiotensin II; CKO; CTL; Cardiac remodeling; FS; HW; Heart; Hypertrophy; IVSd; LC3; LV; LVIDd; LVIDs; LVPWd; LVW; MLC2v; Pressure overload; TAC; cardiac-specific Atg5-deficient mice; control mice; end-diastolic interventricular septal thickness; end-diastolic left ventricular internal dimension; end-diastolic left ventricular posterior wall thickness; end-systolic left ventricular internal dimension; fractional shortening; heart weight; left ventricle; left ventricle weight; microtubule-associated protein 1 light chain 3; myosin light chain 2v; thoracic transverse aortic constriction
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Cardiomegalia
/
Ventrículos do Coração
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Japão