Administration of a TLR9 Inhibitor Attenuates the Development and Progression of Heart Failure in Mice
| العنوان: | Administration of a TLR9 Inhibitor Attenuates the Development and Progression of Heart Failure in Mice |
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| المؤلفون: | Ueda, Hiromichi, Yamaguchi, Osamu, Taneike, Manabu, Akazawa, Yasuhiro, Wada-Kobayashi, Haruko, Sugihara, Ryuta, Yorifuji, Hiroki, Nakayama, Hiroyuki, Omiya, Shigemiki, Murakawa, Tomokazu, Sakata, Yasushi, Otsu, Kinya |
| المصدر: | Ueda, H, Yamaguchi, O, Taneike, M, Akazawa, Y, Wada-Kobayashi, H, Sugihara, R, Yorifuji, H, Nakayama, H, Omiya, S, Murakawa, T, Sakata, Y & Otsu, K 2019, ' Administration of a TLR9 inhibitor attenuates the development and progression of heart failure in mice ', JACC: Basic to Translational Science, vol. 4, no. 3, 10, pp. 348-363 . https://doi.org/10.1016/j.jacbts.2019.01.002Test JACC: Basic to Translational Science |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | TNF, tumor necrosis factor, CpG ODN, unmethylated cytidine-phosphate-guanosine containing oligodeoxynucleotide, mRNA, messenger ribonucleic acid, IVSd, end-diastolic interventricular septal wall thickness, EdU, 5-ethynyl-2′-deoxyuridine, LAMP, lysosome-associated membrane protein, heart failure, Toll-like receptor 9, pressure overload, E6446, (6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole), LC, microtubule-associated protein light chain, IL, interleukin, mitochondria, PRECLINICAL RESEARCH, DNA, deoxyribonucleic acid, CCCP, carbonyl cyanide m-chlorophenyl hydrazine, LPS, lipopolysaccharide, TAC, transverse aortic constriction, LV, left ventricular, CpG, cytidine-phosphate-guanosine, TLR, Toll-like receptor |
| الوصف: | Visual Abstract Highlights • Under pressure overload, mitochondrial deoxyribonucleic acid containing the unmethylated cytidine-phosphate-guanosine motif is accumulated in cardiomyocytes and stimulates Toll-like receptor 9, resulting in inflammation and heart failure. • Treatment with E6446, (6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole), a specific Toll-like receptor 9 inhibitor, prevented the development and slowed the progression of left ventricular dilatation and cardiac dysfunction in mice after pressure overload. • E6446 attenuated the inflammatory responses in the pressure-overloaded mouse heart, even though the accumulation of mitochondrial deoxyribonucleic acid in cardiomyocytes was observed. • E6446 could be a new therapeutic agent against heart failure. Summary Mitochondrial deoxyribonucleic acid, containing the unmethylated cytidine-phosphate-guanosine motif, stimulates Toll-like receptor 9 to induce inflammation and heart failure. A small chemical, E6446 [(6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole)], is a specific Toll-like receptor 9 inhibitor in cardiomyocytes. In this study, we showed that E6446 exerts beneficial effects for the prevention and treatment of pressure overload–induced heart failure in mice. When administered before the operation and chronically thereafter, E6446 prevented the development of left ventricular dilatation as well as cardiac dysfunction, fibrosis, and inflammation. Furthermore, when administered after the manifestation of cardiac dysfunction, E6446 slowed progression of cardiac remodeling. Thus, the inhibitor may be a novel therapeutic agent for treating patients with heart failure. |
| وصف الملف: | application/pdf |
| تدمد: | 2452-302X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::ca33da6ef88468933e5d22ad3c0a67d9Test https://pubmed.ncbi.nlm.nih.gov/31312759Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....ca33da6ef88468933e5d22ad3c0a67d9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2452302X |
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