Nicotinic-acid derivative BGP-15 improves diastolic function in a rabbit model of atherosclerotic cardiomyopathy
Background and purpose: Small molecule BGP-15 has been reported to alleviate signs of heart failure and improve muscle function in murine models. Here, we investigated the acute and chronic effects of BGP-15 in a rabbit model of atherosclerotic cardiomyopathy. Experimental approach: Rabbits were mai...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2022
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| Sorozat: | BRITISH JOURNAL OF PHARMACOLOGY
179 No. 10 |
| Tárgyszavak: | |
| doi: | 10.1111/bph.15749 |
| mtmt: | 32555207 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/29853 |
| LEADER | 03237nab a2200433 i 4500 | ||
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| 001 | publ29853 | ||
| 005 | 20240313093419.0 | ||
| 008 | 240313s2022 hu o 0|| eng d | ||
| 022 | |a 0007-1188 | ||
| 024 | 7 | |a 10.1111/bph.15749 |2 doi | |
| 024 | 7 | |a 32555207 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a eng | ||
| 100 | 1 | |a Priksz Dániel | |
| 245 | 1 | 0 | |a Nicotinic-acid derivative BGP-15 improves diastolic function in a rabbit model of atherosclerotic cardiomyopathy |h [elektronikus dokumentum] / |c Priksz Dániel |
| 260 | |c 2022 | ||
| 300 | |a 2240-2258 | ||
| 490 | 0 | |a BRITISH JOURNAL OF PHARMACOLOGY |v 179 No. 10 | |
| 520 | 3 | |a Background and purpose: Small molecule BGP-15 has been reported to alleviate signs of heart failure and improve muscle function in murine models. Here, we investigated the acute and chronic effects of BGP-15 in a rabbit model of atherosclerotic cardiomyopathy. Experimental approach: Rabbits were maintained on standard chow (Control) or atherogenic diet (HC) for 16 weeks. BGP-15 was administered intravenously (once) or orally (for 16 weeks), to assess acute and chronic effects. Cardiac function was evaluated by echocardiography, endothelium-dependent vasorelaxation was assessed, and key molecules of the protein kinase G (PKG) axis were examined by ELISA and Western blot. Passive force generation was investigated in skinned cardiomyocytes. Key results: Both acute and chronic BGP-15 treatment improved the diastolic performance of the diseased heart, however, vasorelaxation and serum lipid markers were unaffected. Myocardial cGMP levels were elevated in the BGP-15-treated group, along with preserved PKG activity and increased phospholamban Ser16-phosphorylation. PDE5 expression decreased in the BGP-15-treated group, and the substance inhibited PDE1 enzyme. Cardiomyocyte passive tension reduced in BGP-15-treated rabbits, the ratio of titin N2BA/N2B isoforms increased, and PKG-dependent N2B-titin phosphorylation elevated in the BGP-15-treated group. Conclusions and implications: Here we report that BGP-15-treatment improves diastolic function, reduces cardiomyocyte stiffness, and restores titin compliance in a rabbit model of atherosclerotic cardiomyopathy by increasing the activity of the cGMP-PKG axis. As BGP-15 is proven to be safe, it may have clinical value in the treatment of diastolic dysfunction. | |
| 650 | 4 | |a Biológiai tudományok | |
| 700 | 0 | 1 | |a Lampé Nóra |e aut |
| 700 | 0 | 1 | |a Kovács Árpád |e aut |
| 700 | 0 | 1 | |a Herwig Melissa |e aut |
| 700 | 0 | 1 | |a Bombicz Mariann |e aut |
| 700 | 0 | 1 | |a Varga Balázs |e aut |
| 700 | 0 | 1 | |a Wilisicz Tician |e aut |
| 700 | 0 | 1 | |a Szilvássy Judit |e aut |
| 700 | 0 | 1 | |a Pósa Anikó |e aut |
| 700 | 0 | 1 | |a Kiss Rita |e aut |
| 700 | 0 | 1 | |a Gesztelyi Rudolf |e aut |
| 700 | 0 | 1 | |a Ráduly Arnold |e aut |
| 700 | 0 | 1 | |a Szekeres Réka Mária |e aut |
| 700 | 0 | 1 | |a Sieme Marcel |e aut |
| 700 | 0 | 1 | |a Papp Zoltán |e aut |
| 700 | 0 | 1 | |a Tóth Attila |e aut |
| 700 | 0 | 1 | |a Hamdani Nazha |e aut |
| 700 | 0 | 1 | |a Szilvássy Zoltán |e aut |
| 700 | 0 | 1 | |a Juhász Béla |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/29853/1/BritishJPharmacology-203255520721-Priksz-NicotinicacidderivativeBGP15improvesdiastolicfunctioninarabbitmodelof.pdf |z Dokumentum-elérés |