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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.

التفاصيل البيبلوغرافية
العنوان: Sacubitril/valsartan ameliorates cardiac function and ventricular remodeling in CHF rats via the inhibition of the tryptophan/kynurenine metabolism and inflammation.
المؤلفون: Gan J; School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China., Wang Y; School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China., Deng Y; School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China., Zhang J; School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China., Wang S; School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China., Jiang X; School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China., Guo M; School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. tcmguo1007@tjutcm.edu.cn., Song L; School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China. sll0204@163.com.
المصدر: Scientific reports [Sci Rep] 2024 May 29; Vol. 14 (1), pp. 12377. Date of Electronic Publication: 2024 May 29.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: 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, Animals ; Rats ; Male ; Disease Models, Animal ; Natriuretic Peptide, Brain/metabolism ; Natriuretic Peptide, Brain/blood ; Rats, Sprague-Dawley
مستخلص: 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.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 21JCQNJC01170 Tianjin Natural Science Foundation; 81774071 National Natural Science Foundation of China
المشرفين على المادة: 0 (Aminobutyrates)
WB8FT61183 (sacubitril and valsartan sodium hydrate drug combination)
80M03YXJ7I (Valsartan)
0 (Drug Combinations)
0 (Biphenyl Compounds)
343-65-7 (Kynurenine)
8DUH1N11BX (Tryptophan)
0 (Tetrazoles)
114471-18-0 (Natriuretic Peptide, Brain)
تواريخ الأحداث: Date Created: 20240529 Date Completed: 20240530 Latest Revision: 20240601
رمز التحديث: 20240601
مُعرف محوري في PubMed: PMC11136956
DOI: 10.1038/s41598-024-62472-7
PMID: 38811632
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-024-62472-7