Effects of canagliflozin on amino acid metabolism in atherosclerotic mice.
10.3760/cma.j.cn112148-20231009-00275
- Author:
Qing Juan ZUO
1
;
Li Li HE
1
;
Sai MA
2
;
Guo Rui ZHANG
3
;
Ting Ting ZHANG
1
;
Yan WANG
1
;
Yi Fang GUO
1
Author Information
1. Department of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang 050051, China.
2. Department of Pain Medcine, Hebei General Hospital, Shijiazhuang 050051, China.
3. Department of Cardiology, the Third Hospital of Shijiazhuang City, Shijiazhuang 050000, China.
- Publication Type:Journal Article
- MeSH:
Mice;
Animals;
Canagliflozin/therapeutic use*;
Nitric Oxide;
Mice, Knockout;
Mice, Inbred C57BL;
Atherosclerosis/drug therapy*;
Arginine;
Amino Acids;
Apolipoproteins E;
RNA, Messenger;
Plaque, Atherosclerotic;
Azo Compounds
- From:
Chinese Journal of Cardiology
2024;52(1):64-71
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the possible anti-atherosclerotic mechanisms of glucose co-transporter-2 inhibitor canagliflozin. Methods: ApoE-/-mice fed on Western diet were randomly assigned into the model group (n=10) and the canagliflozin group (n=10). C57BL/6J mice fed on normal diet were chosen as the control group (n=10). Mice in the canagliflozin group were gavaged with canagliflozin for 14 weeks. The presence and severity of atherosclerosis were evaluated with HE and oil red O stainings in aortic root section slices. PCR assay was performed to determine the mRNA expression levels of nitric oxide synthase. Hepatic transcriptome analysis and hepatic amino acid detection were conducted using RNA-seq and targeted LC-MS, respectively. Results: HE staining and oil red O staining of the aortic root showed that AS models were successfully established in ApoE-/-mice fed on Western diet for 14 weeks. Canagliflozin alleviated the severity of atherosclerosis in pathology. Hepatic transcriptome analysis indicated that canagliflozin impacted on amino acid metabolism, especially arginine synthesis in ApoE-/-mice. Targeted metabolomics analysis of amino acids showed that canagliflozin reduced hepatic levels of L-serine, L-aspartic acid, tyrosine, L-hydroxyproline, and L-citrulline, but raised the hepatic level of L-arginine. Compared to the model group, the canagliflozin group exhibited higher serum arginine and nitric oxide levels as well as elevated nitric oxide mRNA expression in aortic tissues (P<0.05). Conclusion: Canagliflozin regulated the amino acid metabolism, reduced the levels of glucogenic amino acids,and promoted the synthesis of arginine in atherosclerotic mice.
