Deficiency in adiponectin exaggerates cigarette smoking exposure-induced cardiac contractile dysfunction: Role of autophagy.
Second hand smoke is an independent risk factor for cardiovascular disease. Adiponectin (APN), an adipose-derived adipokine, has been shown to offer cardioprotective effect through an AMPK-dependent manner. This study was designed to evaluate the impact of adiponectin deficiency on second hand smoke-induced cardiac pathology and underlying mechanisms using a mouse model of side-stream smoke exposure. Adult wild-type (WT) and adiponectin knockout (APNKO) mice were placed in a chamber exposed to cigarette smoke for 1 hour daily for 40 days. Echocardiographic, cardiomyocyte function, and intracellular Ca2+ handling were evaluated. Autophagy and apoptosis were examined using western blot. 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) staining was used to evaluate reactive oxygen species (ROS) generation. Masson trichrome staining was employed to measure interstitial fibrosis. Our data revealed that adiponectin deficiency provoked smoke exposure-induced cardiomyopathy (compromised fractional shortening, disrupted cardiomyocyte function and intracellular Ca2+ homeostasis, apoptosis and ROS generation). In addition, these detrimental effects of side-stream smoke were accompanied by defective autophagolysosome formation, the effect of which was exacerbated by adiponectin deficiency. Blocking autophagolysosome formation using bafilomycin A1 (BafA1) negated the cardioprotective effect of rapamycin against smoke extract. Induction of autophagy using rapamycin and AMPKα activation using AICAR rescued against smoke extract-induced myopathic anomalies in APNKO mice. Our data suggest that adiponectin serves as an indispensable cardioprotective factor against side-stream smoke exposure-induced myopathic changes possibly through facilitating autophagolysosome formation.
Department of Cardiology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China; Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA.
Nan
N
Hu
Department of Cardiology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China; Department of Anesthesiology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China.
Lifang
L
Yang
Department of Cardiology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China; Department of Burn and Cutaneous Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China.
Maolong
M
Dong
Department of Cardiology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China; Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA. Electronic address: jren@uwyo.edu.
Jun
J
Ren
Department of Cardiology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China; Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA. Electronic address: zhangym197951@126.com.
Yingmei
Y
Zhang
D052242:Adiponectin / Q000172:deficiency*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*
D052242:Adiponectin; D017382:Reactive Oxygen Species; D002118:Calcium
AMPK; Adiponectin; Autophagy; Cardiomyocyte; Smoking