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

Jota Oyabu, Osamu Yamaguchi, Shungo Hikoso, Toshihiro Takeda, Takafumi Oka, Tomokazu Murakawa, Hiroki Yasui, Hiromichi Ueda, Hiroyuki Nakayama, Manabu Taneike, Shigemiki Omiya, Ajay M. Shah, Kazuhiko Nishida, Kinya Otsu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

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. 

Original languageEnglish
Pages (from-to)787-792
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume441
Issue number4
DOIs
Publication statusPublished - 29 Nov 2013

Keywords

  • Angiotensin II
  • Cardiac remodeling
  • Heart
  • Hypertrophy
  • Pressure overload

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