ANP Increases Zn^(2+)Accumulation During Reperfusion in Ex Vivo and In Vivo Hearts  

作　　者：Yu-ting Ma Tong Laga Chong-ning Zhong Bing-qi Zhuang Hai-lian Quan Lan Hong 

机构地区：[1]Department of Physiology and Pathophysiology,School of Medicine,Yanbian University,Yanji,133002,China [2]Department of General Practice,Affiliated Hospital of Inner Mongolia Minzu University,Tongliao,028000,China

出　　处：《Current Medical Science》2025年第1期35-50,共16页当代医学科学(英文)

基　　金：supported by the National Natural Science Foundation of China(NSFC)(No.82360065 and No.81760047).

摘　　要：Objective Atrial natriuretic peptide(ANP)and Zn^(2+)have been shown to confer cardioprotection against ischemia/reperfu-sion(I/R)injury.Zn^(2+)alleviates myocardial hypertrophy and pulmonary hypertension by regulating ANP expression,but its precise role in ANP-mediated cardioprotection remains unclear.This study aimed to investigate whether ANP protects the heart during reperfusion by modulating Zn^(2+)levels and to explore the underlying mechanisms involved.Methods In this study,we utilized an isolated reperfused heart model in rats,as well as wild-type(WT)and ANP knockout(ANP^(-/-))mouse models,for in vivo I/R experiments.For clinical investigations,plasma samples were collected from 216 patients with ischemia-related diseases.Evans blue and TTC staining,radioimmunoassay,ICP-OES,echocardiography,Hydro-Cy3-mediated ROS detection,and Western blotting were employed to evaluate the effect of ANP on Zn^(2+)homeostasis.Results Plasma ANP levels were significantly elevated in patients with ST-elevation myocardial infarction(STEMI),non-ST-elevation myocardial infarction(NSTEMI),and heart failure(HF).ANP secretion increased during reperfusion,rather than infarction,both ex vivo and in vivo,promoting Zn^(2+)accumulation in reperfused tissue.ANP and Zn^(2+)protected mito-chondria and reduced infarct size;these effects were reversed by the Zn^(2+)chelator TPEN.In WT and ANP^(-/-)mice,EF%and FS%decreased after reperfusion,with ANP^(-/-)mice exhibiting significantly worse cardiac function.ANP pretreatment alone improved cardiac function,but combined pretreatment with ANP and TPEN decreased EF%and FS%while increas-ing LVID.Reperfusion increased ROS levels in both WT and ANP^(-/-)hearts,which were reduced by ANP pretreatment.I/R injury elevated Zn^(2+)transporter 8(ZnT8)expression,an effect that was counteracted by ANP,although this effect was reversed by TPEN.Hypoxia-inducible factor 1-alpha(HIF-1α)expression was elevated in I/R rats and ANP^(-/-)mice,and it was inhibited by both Zn^(2+)and ANP pretreatment.However,the HIF-1

关 键 词：Atrial natriuretic peptide ISCHEMIA/REPERFUSION Zn^(2+) Zn^(2+)transporter Zn2⁺transporter 8 Hypoxia-inducible factor 1-alpha PI3K 

分 类 号：R54[医药卫生—心血管疾病]