title: Mechanical stress triggers cardiomyocyte autophagy through angiotensin II type 1 receptor-mediated p38MAP kinase independently of angiotensin II.
abstract: Angiotensin II (Ang II) type 1 (AT1) receptor is known to mediate a variety of physiological actions of Ang II including autophagy. However, the role of AT1 receptor in cardiomyocyte autophagy triggered by mechanical stress still remains elusive. The aim of this study was therefore to examine whether and how AT1 receptor participates in cardiomyocyte autophagy induced by mechanical stresses. A 48-hour mechanical stretch and a 4-week transverse aorta constriction (TAC) were imposed to cultured cardiomyocytes of neonatal rats and adult male C57B/L6 mice, respectively, to induce cardiomyocyte hypertrophy prior to the assessment of cardiomyocyte autophagy using LC3b-II. Losartan, an AT1 receptor blocker, but not PD123319, the AT2 inhibitor, was found to significantly reduce mechanical stretch-induced LC3b-II upregulation. Moreover, inhibition of p38MAP kinase attenuated not only mechanical stretch-induced cardiomyocyte hypertrophy but also autophagy. To the contrary, inhibition of ERK and JNK suppressed cardiac hypertrophy but not autophagy. Intriguingly, mechanical stretch-induced autophagy was significantly inhibited by Losartan in the absence of Ang II. Taken together, our results indicate that mechanical stress triggers cardiomyocyte autophagy through AT1 receptor-mediated activation of p38MAP kinase independently of Ang II.
authors.affiliation: Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Chuyi
authors.initials: C
authors.lastname: Tang
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Science, Fudan University, Shanghai, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Science, Fudan University, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Science, Fudan University, Shanghai, China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Weng
authors.affiliation: Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Science, Fudan University, Shanghai, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
authors.affiliation: Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xuebo
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institute of Biomedical Science, Fudan University, Shanghai, China.
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001343:Autophagy; D001696:Biomechanical Phenomena; D019556:COS Cells; D006332:Cardiomegaly / Q000201:enzymology / Q000473:pathology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000502:physiology*; D051381:Rats; D013312:Stress, Physiological; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C119712:Agtrap protein, mouse; D000804:Angiotensin II; D048051:p38 Mitogen-Activated Protein Kinases