Chloroquine improves left ventricle diastolic function in streptozotocin-induced diabetic mice.
Diabetes is a potent risk factor for heart failure with preserved ejection fraction (HFpEF). Autophagy can be activated under pathological conditions, including diabetic cardiomyopathy. The therapeutic effects of chloroquine (CQ), an autophagy inhibitor, on left ventricle function in streptozotocin (STZ)-induced diabetic mice were investigated. The cardiac function, light chain 3 (LC3)-II/LC3-I ratio, p62, beclin 1, reactive oxygen species, apoptosis, and fibrosis were measured 14 days after CQ (ip 60 mg/kg/d) administration. In STZ-induced mice, cardiac diastolic function was decreased significantly with normal ejection fraction. CQ significantly ameliorated cardiac diastolic function in diabetic mice with HFpEF. In addition, CQ decreased the autophagolysosomes, cardiomyocyte apoptosis, and cardiac fibrosis but increased LC3-II and p62 expressions. These results suggested that CQ improved the cardiac diastolic function by inhibiting autophagy in STZ-induced HFpEF mice. Autophagic inhibitor CQ might be a potential therapeutic agent for HFpEF.
Department of Pharmacology, Guangzhou Medical University, Guangzhou, People's Republic of China.
Xun
X
Yuan
Department of Pharmacology, Guangzhou Medical University, Guangzhou, People's Republic of China.
Yi-Chuan
YC
Xiao
Department of Pharmacology, Guangzhou Medical University, Guangzhou, People's Republic of China.
Gui-Ping
GP
Zhang
Department of Pharmacology, Guangzhou Medical University, Guangzhou, People's Republic of China.
Ning
N
Hou
Department of Pharmacology, Guangzhou Medical University, Guangzhou, People's Republic of China.
Xiao-Qian
XQ
Wu
Department of Pharmacology, Guangzhou Medical University, Guangzhou, People's Republic of China.
Wen-Liang
WL
Chen
Department of Pharmacology, Guangzhou Medical University, Guangzhou, People's Republic of China.
Jian-Dong
JD
Luo
Department of Pharmacology, Guangzhou Medical University, Guangzhou, People's Republic of China.
Gen-Shui
GS
Zhang
D000818:Animals; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013311:Streptozocin; D016277:Ventricular Function, Left
D013311:Streptozocin; D002738:Chloroquine
HFpEF; autophagy; chloroquine; diabetic cardiomyopathy; diastolic function; type 1 diabetes mellitus