Autophagy-mediated degradation is necessary for regression of cardiac hypertrophy during ventricular unloading

TY - JOUR

T1 - Autophagy-mediated degradation is necessary for regression of cardiac hypertrophy during ventricular unloading

AU - Oyabu, Jota

AU - Yamaguchi, Osamu

AU - Hikoso, Shungo

AU - Takeda, Toshihiro

AU - Oka, Takafumi

AU - Murakawa, Tomokazu

AU - Yasui, Hiroki

AU - Ueda, Hiromichi

AU - Nakayama, Hiroyuki

AU - Taneike, Manabu

AU - Omiya, Shigemiki

AU - Shah, Ajay M.

AU - Nishida, Kazuhiko

AU - Otsu, Kinya

N1 - © 2013.

PY - 2013/11/29

Y1 - 2013/11/29

N2 - 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. 

AB - 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. 

KW - Angiotensin II

KW - Cardiac remodeling

KW - Heart

KW - Hypertrophy

KW - Pressure overload

UR - http://www.scopus.com/inward/record.url?scp=84888839943&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2013.10.135

DO - 10.1016/j.bbrc.2013.10.135

M3 - Article

C2 - 24211573

AN - SCOPUS:84888839943

SN - 0006-291X

VL - 441

SP - 787

EP - 792

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -