Angiotensin Ⅱ type 1a receptor knockout ameliorates high-fat diet induced cardiac dysfunction by attenuating ferroptosis
- VernacularTitle:血管紧张素Ⅱ 1a型受体基因敲除通过减轻铁死亡来改善高脂饮食诱导的心功能障碍
- Author:
Xiao-xiao YIN
1
;
Jin WANG
1
;
Ai-yun LI
1
;
Li-qing WANG
1
;
Min GOU
1
;
Xiang-ying JIAO
1
Author Information
- Publication Type:Journal Article
- Keywords: renin-angiotensin system; angiotensin type 1a receptor; high-fat diet; cardiac dysfunction; ferroptosis; oxidative stress
- From: Chinese Pharmacological Bulletin 2025;41(11):2105-2112
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effect of angioten-sin Ⅱ type 1a receptor(AT1aR)knockout on cardiac dysfunction in rats with obesity and its possible molecu-lar mechanism.Methods SD rats(n=24)were used to generated the whole-body AT1 aR-deficiency rats by sgRNA and the CRISPR/Cas9 system,and the obesity model was constructed by feeding with high-fat diet(HFD).They were divided into four groups:wildtype(WT)and knockout(KO)groups with nor-mal feeding and their respective high-fat diets groups.Color ultrasound diagnostic instrument was uses to e-valuate the cardiac function;oil red O staining was a-dopted to stain the myocardial lipids;RT-PCR was used to detect the levels of GPX4 and Ptgs2 genes in myocardial tissue.Western blot was employed to detect the expression of GPX4,ferritin,Nrf2,HO-1 and NQO1 in rat myocardial tissue.ELISA and other kits were used to determine the lipid contents in serum and myocardium.Results It was found that high-fat feed-ing caused cardiac dysfunction,serum lipid disorders,oxidative stress and ferroptosis in SD rats.However,these changes were attenuated in AT1aR knockout rats fed with high-fat diet.Furthermore,compared with WT-HFD group,KO-HFD rats showed enhanced acti-vation of the Nrf2/HO-1 pathway in the myocardium,reduced ferroptosis,decreased lipid accumulation,and reduced cardiac dysfunction.Conclusion AT1aR knockout can improve HFD-induced cardiac dysfunc-tion by enhancing antioxidant capacity and reducing the degree of ferroptosis.
