Induction Of Endoplasmic Reticulum Stress And Variation In Expression Levels Of ZIP14 In Heart Failure With Preserved Ejection Fraction Rat Heart

Objective To establish a model of heart failure with preserved ejection fraction(HFp EF)in rats and to measure variation in zinc contents and expression levels of Zip14 in myocardial of HFp EF rats.Besides,to confirm the existences of endoplasmic reticulum stress and inflammation.Methods In order to establish HFp EF rat model,we choose Dahl salt-sensitive(DSS)rats and fed a high salt diet to experimental group.However,the control group was fed a normal salt diet.The content of sodium chloride in high salt feed was 8%,while the normal diet group was 0.3%.The remaining feed ingredients and feeding conditions are same.Blood pressure and heart rate were measured by the noninvasive blood pressure detector every two weeks.In sixth weeks,12 weeks and 19 weeks respectively,the rats were detected by animal specific ultrasound.To detect variation in zinc contents and expression levels of Zip14 in myocardial of HFp EF rats,The left ventricular myocardium specimens were extracted from the successful HFp EF model rat and the control group of corresponding time.Immediately myocardial specimens stored at-80 ? until use.The zinc levels of specimens were measured by Inductively Coupled Plasma Optical Emission Spectroscopy(ICP-OES).RT-fq-PCR and Western blot were used to detect m RNA and protein expression of Zip14 in the myocardium.To clarify the existences of endoplasmic reticulum stress and inflammation,RT-fq-PCR was used to detect m RNA expression levels of signal molecules of endoplasmic reticulum stress in myocardium,such as ATF6,ATF4,CHOP,Bip and x BPI.Western blot was used to detect protein expression levels of CHOP,Bip and inflammation transcription factor NF-?B p65.Results1.the mean systolic blood pressure(SBP),LVM and LVM/W in HS-group was significantly higher than that in the NS-group but did not,however,show a significant difference with EF in 19 th weeks.2.Compared to the control group,Zip14 m RNA and protein expression levels in the HFp EF rat heart were markedly increased.Besides,the zinc contents in rat heart tissue was significantly increased in HFp EF group when compared to control group.3.The m RNA expression levels of ATF6,ATF4,CHOP,Bip and x BPI was significantly higher in HFp EF-group than control-group.The expression levels of CHOP,Bip and NF-?B p65 in HFp EF rat heart were significantly increased compared to those of the controls.Conclusion:In conclusion,zinc accumulation of the HFp EF rat heart were correlated with up-regulation of Zip14 expression,ER stress and inflammatory.However,the exact mechanism of these interactions needs to be further investigated.