title: Autophagy-mediated degradation is necessary for regression of cardiac hypertrophy during ventricular unloading.
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.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Jota
authors.initials: J
authors.lastname: Oyabu
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
authors.forename: Shungo
authors.initials: S
authors.lastname: Hikoso
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takeda
authors.forename: Takafumi
authors.initials: T
authors.lastname: Oka
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Murakawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yasui
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ueda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
authors.forename: Manabu
authors.initials: M
authors.lastname: Taneike
authors.forename: Shigemiki
authors.initials: S
authors.lastname: Omiya
authors.forename: Ajay M
authors.initials: AM
authors.lastname: Shah
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishida
authors.forename: Kinya
authors.initials: K
authors.lastname: Otsu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D006332:Cardiomegaly / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000503:physiopathology*; D051379:Mice; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D000804:Angiotensin II
keywords: 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