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Sacubitril/valsartan ameliorates cardiac function and ventricular remodeling in CHF rats via the inhibition of the tryptophan/kynurenine metabolism and inflammation.
- Source :
-
Scientific reports [Sci Rep] 2024 May 29; Vol. 14 (1), pp. 12377. Date of Electronic Publication: 2024 May 29. - Publication Year :
- 2024
-
Abstract
- Sacubitril/valsartan has been highly recognized as a treatment for Chronic heart failure (CHF). Its potential cardioprotective benefits and mechanisms, however, remain to be explored. Metabolomics can be used to identify the metabolic characteristics and related markers, as well as the influence of drugs, thereby opening up the new mechanism for sacubitril/valsartan therapy in CHF disease. In this study, the ligation of left anterior descending and exhaustive swimming were used to induce a rat model of CHF after myocardial infarction. The efficacy was appraised with echocardiography, serum NT-proBNP, and histopathologica. UPLC-Q/TOF-MS combined with multivariate statistical analysis approach were used to analyze the effect of sacubitril/valsartan on CHF rats. RT-qPCR and western blot were performed to investigate the tryptophan/kynurenine metabolism pathway. Accordingly, the basal cardiac function were increased, while the serum NT-proBNP and collagen volume fraction decreased in CHF rats with sacubitril/valsartan. Sacubitril/valsartan regulated the expression of kynurenine et.al 8 metabolomic biomarkers in CHF rats serum, and it contributed to the cardioprotective effects through tryptophan metabolism pathway. In addition, the mRNA and protein expression of the indoleamine 2,3-dioxygenase (IDO) in the myocardial tissue of CHF rats, were down-regulated by sacubitril/valsartan, which was the same with the IL-1β, IFN-γ, TNF-α, COX-2, and IL-6 mRNA expression, and IL-1β, IFN-γ, and TNF-α expression in serum. In conclusion, sacubitril/valsartan can ameliorate cardiac function and ventricular remodeling in CHF rats, at least in part through inhibition of tryptophan/kynurenine metabolism.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Rats
Male
Disease Models, Animal
Natriuretic Peptide, Brain metabolism
Natriuretic Peptide, Brain blood
Rats, Sprague-Dawley
Aminobutyrates pharmacology
Valsartan pharmacology
Drug Combinations
Biphenyl Compounds pharmacology
Ventricular Remodeling drug effects
Kynurenine metabolism
Heart Failure drug therapy
Heart Failure metabolism
Tryptophan metabolism
Tetrazoles pharmacology
Inflammation drug therapy
Inflammation metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 38811632
- Full Text :
- https://doi.org/10.1038/s41598-024-62472-7