Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction

Schimmel, K. (Katharina)|||/items/db398c60-e014-48da-843a-880afc77498d; Jung, M. (Mira)|||/items/55431b8b-35ee-4dcf-8e5e-8b08e6e2827c; Foinquinos, A. (Ariana)|||/items/2999aa62-73a3-42b7-99b2-c2e69454aef6; San-José-Enériz, G. (Gorka)|||/items/362ac8c3-5d50-4383-9fc1-7abbed048387; Beaumont-Ezcurra, F.J. (Francisco Javier)|||/items/6824d098-1970-4668-9169-8f1f3352e015; Bock, K. (Katharina)|||/items/bc845b4d-826c-4062-b66b-07dc2b56c3f7; Grote-Levi, L. (Lea)|||/items/e7838932-cd4e-4617-bb71-e73c81fa34c4; Xiao, K. (Ke)|||/items/efd36424-9892-4b59-95ac-381ad6f0b49d; Bär, C. (Christian)|||/items/e18d378a-d1b0-49e0-b17c-cbc2446db784; Pfanne, A. (Angelika)|||/items/58cec70d-6f74-48d8-a22d-cceda444fc50; Just, A. (Annette)|||/items/94da7ba3-4871-4557-bb7c-a43777891914; Zimmer, K. (Karina)|||/items/fc6d04ba-cbac-4373-8d36-8d3f9d2c9533; Ngoy, S. (Soeun)|||/items/b56c93cf-229a-4f54-91b6-41c70fad5b2c; Lopez-Salazar, M.B. (María Begoña)|||/items/153e0e37-14b0-403e-afab-8af00c4edde0; Ravassa-Albéniz, S. (Susana)|||/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1; Samolovac, S. (Sabine)|||/items/afb76b87-7740-4b3d-9c34-8051bd6a20c8; Janssen-Peters, H. (Heike)|||/items/1afa51e2-5698-488c-a15c-4ccdc6378506; Remke, J. (Janet)|||/items/94a9afeb-8615-4ef2-8fab-5ec4b87e29ab; Scherf, K. (Kristian)|||/items/f11c61fe-a5f7-477d-8ab7-03c42b0fb03d; Dangwal, S. (Seema)|||/items/7551716b-ff32-4d80-819a-c3e21b3f1cd8; Piccoli, M.T. (Maria-Teresa)|||/items/f16f01e7-db3f-428c-91ec-d74873ca3647; Kleemiss, F. (Felix)|||/items/e79b7681-1194-4143-9932-7b8842be822d; Kreutzer, F.P. (Fabian Philipp)|||/items/b147d259-b4bb-4888-bca6-2d361089dcb0; Kenneweg, F. (Franziska)|||/items/25fd4ebb-ce36-4e47-995c-91f2e1b9ed90; Leonardy, J. (Julia)|||/items/6f6e8618-8901-407b-bdfe-8d26486a0a4f; Hobuss, L. (Lisa)|||/items/9ea2b6f7-fbfc-4d19-a0fa-8cffd8dd33d0; Santer, L. (Laura)|||/items/a3c367f6-93c7-4ab8-9e2d-1fa08f5f7e30; Do, Q.T. (Quoc-Tuan)|||/items/8dd0ef69-394b-43d7-a17a-c29c61ce1027; Geffers, R. (Robert)|||/items/007f5c8f-ce2d-40ff-b6e4-7659912b33ed; Braesen, J.H. (Jan Hinrich)|||/items/b499fca6-9ca9-45c6-8b56-f7531e7c8043; Schmitz, J. (Jessica)|||/items/ccd4ceeb-611a-4405-8427-1a7a01c1bde3; Brandenberger, C. (Christina)|||/items/565d2c4a-7fea-4e7e-8aa2-f0332717280d; Müller, D.N. (Dominik N.)|||/items/9bbb7bf5-2c89-40ef-8742-22b5759d022c; Wilck, N. (Nicola)|||/items/2b9af0ea-e805-422b-a411-26aed9607e3c; Kaever, V. (Volkhard)|||/items/5e9e0e4f-1d3f-41db-8815-f8d6ef95d608; Bähre, H. (Heike)|||/items/b0975de2-400a-4c5f-8aed-aefef4641e9e; Batkai, S. (Sandor)|||/items/a219d6b4-89a4-4f08-bf5f-55816dec3a22; Fiedler, J. (Jan)|||/items/ef7f7706-d97b-435c-8d15-485034293bea; Alexander, K.M. (Kevin M.)|||/items/ae5ef3ee-e558-46a8-b37f-3832a812e695; Wertheim, B.M. (Bradley M.)|||/items/c4effae0-40c1-47b8-b218-16cede54c3a2; Fisch, S. (Sudeshna)|||/items/3086287b-fe51-43d0-8303-c009187a5853; Liao, R. (Ronglih)|||/items/a9dce0fe-8681-43d5-8dbe-ac02af7531e0; Diez, J. (Javier)|||/items/adeda0be-cebc-4240-899c-ab26f05dea9c; Gonzalez, A. (Arantxa)|||/items/9c64c0f4-66b4-4b51-8593-0e50c091a515; Thum, T. (Thomas)|||/items/c2b8a6be-55a5-4810-afe7-c5b019ebb02a

Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction

BACKGROUND: Myocardial fibrosis is a hallmark of cardiac remodeling and functionally involved in heart failure development, a leading cause of deaths worldwide. Clinically, no therapeutic strategy is available that specifically attenuates maladaptive responses of cardiac fibroblasts, the effector ce...

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Detalles Bibliográficos
Autores:	Schimmel, K. (Katharina)\|\|\|/items/db398c60-e014-48da-843a-880afc77498d, Jung, M. (Mira)\|\|\|/items/55431b8b-35ee-4dcf-8e5e-8b08e6e2827c, Foinquinos, A. (Ariana)\|\|\|/items/2999aa62-73a3-42b7-99b2-c2e69454aef6, San-José-Enériz, G. (Gorka)\|\|\|/items/362ac8c3-5d50-4383-9fc1-7abbed048387, Beaumont-Ezcurra, F.J. (Francisco Javier)\|\|\|/items/6824d098-1970-4668-9169-8f1f3352e015, Bock, K. (Katharina)\|\|\|/items/bc845b4d-826c-4062-b66b-07dc2b56c3f7, Grote-Levi, L. (Lea)\|\|\|/items/e7838932-cd4e-4617-bb71-e73c81fa34c4, Xiao, K. (Ke)\|\|\|/items/efd36424-9892-4b59-95ac-381ad6f0b49d, Bär, C. (Christian)\|\|\|/items/e18d378a-d1b0-49e0-b17c-cbc2446db784, Pfanne, A. (Angelika)\|\|\|/items/58cec70d-6f74-48d8-a22d-cceda444fc50, Just, A. (Annette)\|\|\|/items/94da7ba3-4871-4557-bb7c-a43777891914, Zimmer, K. (Karina)\|\|\|/items/fc6d04ba-cbac-4373-8d36-8d3f9d2c9533, Ngoy, S. (Soeun)\|\|\|/items/b56c93cf-229a-4f54-91b6-41c70fad5b2c, Lopez-Salazar, M.B. (María Begoña)\|\|\|/items/153e0e37-14b0-403e-afab-8af00c4edde0, Ravassa-Albéniz, S. (Susana)\|\|\|/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1, Samolovac, S. (Sabine)\|\|\|/items/afb76b87-7740-4b3d-9c34-8051bd6a20c8, Janssen-Peters, H. (Heike)\|\|\|/items/1afa51e2-5698-488c-a15c-4ccdc6378506, Remke, J. (Janet)\|\|\|/items/94a9afeb-8615-4ef2-8fab-5ec4b87e29ab, Scherf, K. (Kristian)\|\|\|/items/f11c61fe-a5f7-477d-8ab7-03c42b0fb03d, Dangwal, S. (Seema)\|\|\|/items/7551716b-ff32-4d80-819a-c3e21b3f1cd8, Piccoli, M.T. (Maria-Teresa)\|\|\|/items/f16f01e7-db3f-428c-91ec-d74873ca3647, Kleemiss, F. (Felix)\|\|\|/items/e79b7681-1194-4143-9932-7b8842be822d, Kreutzer, F.P. (Fabian Philipp)\|\|\|/items/b147d259-b4bb-4888-bca6-2d361089dcb0, Kenneweg, F. (Franziska)\|\|\|/items/25fd4ebb-ce36-4e47-995c-91f2e1b9ed90, Leonardy, J. (Julia)\|\|\|/items/6f6e8618-8901-407b-bdfe-8d26486a0a4f, Hobuss, L. (Lisa)\|\|\|/items/9ea2b6f7-fbfc-4d19-a0fa-8cffd8dd33d0, Santer, L. (Laura)\|\|\|/items/a3c367f6-93c7-4ab8-9e2d-1fa08f5f7e30, Do, Q.T. (Quoc-Tuan)\|\|\|/items/8dd0ef69-394b-43d7-a17a-c29c61ce1027, Geffers, R. (Robert)\|\|\|/items/007f5c8f-ce2d-40ff-b6e4-7659912b33ed, Braesen, J.H. (Jan Hinrich)\|\|\|/items/b499fca6-9ca9-45c6-8b56-f7531e7c8043, Schmitz, J. (Jessica)\|\|\|/items/ccd4ceeb-611a-4405-8427-1a7a01c1bde3, Brandenberger, C. (Christina)\|\|\|/items/565d2c4a-7fea-4e7e-8aa2-f0332717280d, Müller, D.N. (Dominik N.)\|\|\|/items/9bbb7bf5-2c89-40ef-8742-22b5759d022c, Wilck, N. (Nicola)\|\|\|/items/2b9af0ea-e805-422b-a411-26aed9607e3c, Kaever, V. (Volkhard)\|\|\|/items/5e9e0e4f-1d3f-41db-8815-f8d6ef95d608, Bähre, H. (Heike)\|\|\|/items/b0975de2-400a-4c5f-8aed-aefef4641e9e, Batkai, S. (Sandor)\|\|\|/items/a219d6b4-89a4-4f08-bf5f-55816dec3a22, Fiedler, J. (Jan)\|\|\|/items/ef7f7706-d97b-435c-8d15-485034293bea, Alexander, K.M. (Kevin M.)\|\|\|/items/ae5ef3ee-e558-46a8-b37f-3832a812e695, Wertheim, B.M. (Bradley M.)\|\|\|/items/c4effae0-40c1-47b8-b218-16cede54c3a2, Fisch, S. (Sudeshna)\|\|\|/items/3086287b-fe51-43d0-8303-c009187a5853, Liao, R. (Ronglih)\|\|\|/items/a9dce0fe-8681-43d5-8dbe-ac02af7531e0, Diez, J. (Javier)\|\|\|/items/adeda0be-cebc-4240-899c-ab26f05dea9c, Gonzalez, A. (Arantxa)\|\|\|/items/9c64c0f4-66b4-4b51-8593-0e50c091a515, Thum, T. (Thomas)\|\|\|/items/c2b8a6be-55a5-4810-afe7-c5b019ebb02a
Tipo de recurso:	artículo
Fecha de publicación:	2020
País:	España
Institución:	Universidad de Navarra
Repositorio:	Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:	inglés
OAI Identifier:	oai:dadun.unav.edu:10171/67169
Acceso en línea:	https://hdl.handle.net/10171/67169
Access Level:	acceso abierto
Palabra clave:	Diastole Fibrosis Hypertension microRNAs

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oai_identifier_str	oai:dadun.unav.edu:10171/67169
network_acronym_str	ES
network_name_str	España
repository_id_str
dc.title.none.fl_str_mv	Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction
title	Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction
spellingShingle	Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction Schimmel, K. (Katharina)\|\|\|/items/db398c60-e014-48da-843a-880afc77498d Diastole Fibrosis Hypertension microRNAs
title_short	Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction
title_full	Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction
title_fullStr	Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction
title_full_unstemmed	Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction
title_sort	Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction
dc.creator.none.fl_str_mv	Schimmel, K. (Katharina)\|\|\|/items/db398c60-e014-48da-843a-880afc77498d Jung, M. (Mira)\|\|\|/items/55431b8b-35ee-4dcf-8e5e-8b08e6e2827c Foinquinos, A. (Ariana)\|\|\|/items/2999aa62-73a3-42b7-99b2-c2e69454aef6 San-José-Enériz, G. (Gorka)\|\|\|/items/362ac8c3-5d50-4383-9fc1-7abbed048387 Beaumont-Ezcurra, F.J. (Francisco Javier)\|\|\|/items/6824d098-1970-4668-9169-8f1f3352e015 Bock, K. (Katharina)\|\|\|/items/bc845b4d-826c-4062-b66b-07dc2b56c3f7 Grote-Levi, L. (Lea)\|\|\|/items/e7838932-cd4e-4617-bb71-e73c81fa34c4 Xiao, K. (Ke)\|\|\|/items/efd36424-9892-4b59-95ac-381ad6f0b49d Bär, C. (Christian)\|\|\|/items/e18d378a-d1b0-49e0-b17c-cbc2446db784 Pfanne, A. (Angelika)\|\|\|/items/58cec70d-6f74-48d8-a22d-cceda444fc50 Just, A. (Annette)\|\|\|/items/94da7ba3-4871-4557-bb7c-a43777891914 Zimmer, K. (Karina)\|\|\|/items/fc6d04ba-cbac-4373-8d36-8d3f9d2c9533 Ngoy, S. (Soeun)\|\|\|/items/b56c93cf-229a-4f54-91b6-41c70fad5b2c Lopez-Salazar, M.B. (María Begoña)\|\|\|/items/153e0e37-14b0-403e-afab-8af00c4edde0 Ravassa-Albéniz, S. (Susana)\|\|\|/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1 Samolovac, S. (Sabine)\|\|\|/items/afb76b87-7740-4b3d-9c34-8051bd6a20c8 Janssen-Peters, H. (Heike)\|\|\|/items/1afa51e2-5698-488c-a15c-4ccdc6378506 Remke, J. (Janet)\|\|\|/items/94a9afeb-8615-4ef2-8fab-5ec4b87e29ab Scherf, K. (Kristian)\|\|\|/items/f11c61fe-a5f7-477d-8ab7-03c42b0fb03d Dangwal, S. (Seema)\|\|\|/items/7551716b-ff32-4d80-819a-c3e21b3f1cd8 Piccoli, M.T. (Maria-Teresa)\|\|\|/items/f16f01e7-db3f-428c-91ec-d74873ca3647 Kleemiss, F. (Felix)\|\|\|/items/e79b7681-1194-4143-9932-7b8842be822d Kreutzer, F.P. (Fabian Philipp)\|\|\|/items/b147d259-b4bb-4888-bca6-2d361089dcb0 Kenneweg, F. (Franziska)\|\|\|/items/25fd4ebb-ce36-4e47-995c-91f2e1b9ed90 Leonardy, J. (Julia)\|\|\|/items/6f6e8618-8901-407b-bdfe-8d26486a0a4f Hobuss, L. (Lisa)\|\|\|/items/9ea2b6f7-fbfc-4d19-a0fa-8cffd8dd33d0 Santer, L. (Laura)\|\|\|/items/a3c367f6-93c7-4ab8-9e2d-1fa08f5f7e30 Do, Q.T. (Quoc-Tuan)\|\|\|/items/8dd0ef69-394b-43d7-a17a-c29c61ce1027 Geffers, R. (Robert)\|\|\|/items/007f5c8f-ce2d-40ff-b6e4-7659912b33ed Braesen, J.H. (Jan Hinrich)\|\|\|/items/b499fca6-9ca9-45c6-8b56-f7531e7c8043 Schmitz, J. (Jessica)\|\|\|/items/ccd4ceeb-611a-4405-8427-1a7a01c1bde3 Brandenberger, C. (Christina)\|\|\|/items/565d2c4a-7fea-4e7e-8aa2-f0332717280d Müller, D.N. (Dominik N.)\|\|\|/items/9bbb7bf5-2c89-40ef-8742-22b5759d022c Wilck, N. (Nicola)\|\|\|/items/2b9af0ea-e805-422b-a411-26aed9607e3c Kaever, V. (Volkhard)\|\|\|/items/5e9e0e4f-1d3f-41db-8815-f8d6ef95d608 Bähre, H. (Heike)\|\|\|/items/b0975de2-400a-4c5f-8aed-aefef4641e9e Batkai, S. (Sandor)\|\|\|/items/a219d6b4-89a4-4f08-bf5f-55816dec3a22 Fiedler, J. (Jan)\|\|\|/items/ef7f7706-d97b-435c-8d15-485034293bea Alexander, K.M. (Kevin M.)\|\|\|/items/ae5ef3ee-e558-46a8-b37f-3832a812e695 Wertheim, B.M. (Bradley M.)\|\|\|/items/c4effae0-40c1-47b8-b218-16cede54c3a2 Fisch, S. (Sudeshna)\|\|\|/items/3086287b-fe51-43d0-8303-c009187a5853 Liao, R. (Ronglih)\|\|\|/items/a9dce0fe-8681-43d5-8dbe-ac02af7531e0 Diez, J. (Javier)\|\|\|/items/adeda0be-cebc-4240-899c-ab26f05dea9c Gonzalez, A. (Arantxa)\|\|\|/items/9c64c0f4-66b4-4b51-8593-0e50c091a515 Thum, T. (Thomas)\|\|\|/items/c2b8a6be-55a5-4810-afe7-c5b019ebb02a
author	Schimmel, K. (Katharina)\|\|\|/items/db398c60-e014-48da-843a-880afc77498d
author_facet	Schimmel, K. (Katharina)\|\|\|/items/db398c60-e014-48da-843a-880afc77498d Jung, M. (Mira)\|\|\|/items/55431b8b-35ee-4dcf-8e5e-8b08e6e2827c Foinquinos, A. (Ariana)\|\|\|/items/2999aa62-73a3-42b7-99b2-c2e69454aef6 San-José-Enériz, G. (Gorka)\|\|\|/items/362ac8c3-5d50-4383-9fc1-7abbed048387 Beaumont-Ezcurra, F.J. (Francisco Javier)\|\|\|/items/6824d098-1970-4668-9169-8f1f3352e015 Bock, K. (Katharina)\|\|\|/items/bc845b4d-826c-4062-b66b-07dc2b56c3f7 Grote-Levi, L. (Lea)\|\|\|/items/e7838932-cd4e-4617-bb71-e73c81fa34c4 Xiao, K. (Ke)\|\|\|/items/efd36424-9892-4b59-95ac-381ad6f0b49d Bär, C. (Christian)\|\|\|/items/e18d378a-d1b0-49e0-b17c-cbc2446db784 Pfanne, A. (Angelika)\|\|\|/items/58cec70d-6f74-48d8-a22d-cceda444fc50 Just, A. (Annette)\|\|\|/items/94da7ba3-4871-4557-bb7c-a43777891914 Zimmer, K. (Karina)\|\|\|/items/fc6d04ba-cbac-4373-8d36-8d3f9d2c9533 Ngoy, S. (Soeun)\|\|\|/items/b56c93cf-229a-4f54-91b6-41c70fad5b2c Lopez-Salazar, M.B. (María Begoña)\|\|\|/items/153e0e37-14b0-403e-afab-8af00c4edde0 Ravassa-Albéniz, S. (Susana)\|\|\|/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1 Samolovac, S. (Sabine)\|\|\|/items/afb76b87-7740-4b3d-9c34-8051bd6a20c8 Janssen-Peters, H. (Heike)\|\|\|/items/1afa51e2-5698-488c-a15c-4ccdc6378506 Remke, J. (Janet)\|\|\|/items/94a9afeb-8615-4ef2-8fab-5ec4b87e29ab Scherf, K. (Kristian)\|\|\|/items/f11c61fe-a5f7-477d-8ab7-03c42b0fb03d Dangwal, S. (Seema)\|\|\|/items/7551716b-ff32-4d80-819a-c3e21b3f1cd8 Piccoli, M.T. (Maria-Teresa)\|\|\|/items/f16f01e7-db3f-428c-91ec-d74873ca3647 Kleemiss, F. (Felix)\|\|\|/items/e79b7681-1194-4143-9932-7b8842be822d Kreutzer, F.P. (Fabian Philipp)\|\|\|/items/b147d259-b4bb-4888-bca6-2d361089dcb0 Kenneweg, F. (Franziska)\|\|\|/items/25fd4ebb-ce36-4e47-995c-91f2e1b9ed90 Leonardy, J. (Julia)\|\|\|/items/6f6e8618-8901-407b-bdfe-8d26486a0a4f Hobuss, L. (Lisa)\|\|\|/items/9ea2b6f7-fbfc-4d19-a0fa-8cffd8dd33d0 Santer, L. (Laura)\|\|\|/items/a3c367f6-93c7-4ab8-9e2d-1fa08f5f7e30 Do, Q.T. (Quoc-Tuan)\|\|\|/items/8dd0ef69-394b-43d7-a17a-c29c61ce1027 Geffers, R. (Robert)\|\|\|/items/007f5c8f-ce2d-40ff-b6e4-7659912b33ed Braesen, J.H. (Jan Hinrich)\|\|\|/items/b499fca6-9ca9-45c6-8b56-f7531e7c8043 Schmitz, J. (Jessica)\|\|\|/items/ccd4ceeb-611a-4405-8427-1a7a01c1bde3 Brandenberger, C. (Christina)\|\|\|/items/565d2c4a-7fea-4e7e-8aa2-f0332717280d Müller, D.N. (Dominik N.)\|\|\|/items/9bbb7bf5-2c89-40ef-8742-22b5759d022c Wilck, N. (Nicola)\|\|\|/items/2b9af0ea-e805-422b-a411-26aed9607e3c Kaever, V. (Volkhard)\|\|\|/items/5e9e0e4f-1d3f-41db-8815-f8d6ef95d608 Bähre, H. (Heike)\|\|\|/items/b0975de2-400a-4c5f-8aed-aefef4641e9e Batkai, S. (Sandor)\|\|\|/items/a219d6b4-89a4-4f08-bf5f-55816dec3a22 Fiedler, J. (Jan)\|\|\|/items/ef7f7706-d97b-435c-8d15-485034293bea Alexander, K.M. (Kevin M.)\|\|\|/items/ae5ef3ee-e558-46a8-b37f-3832a812e695 Wertheim, B.M. (Bradley M.)\|\|\|/items/c4effae0-40c1-47b8-b218-16cede54c3a2 Fisch, S. (Sudeshna)\|\|\|/items/3086287b-fe51-43d0-8303-c009187a5853 Liao, R. (Ronglih)\|\|\|/items/a9dce0fe-8681-43d5-8dbe-ac02af7531e0 Diez, J. (Javier)\|\|\|/items/adeda0be-cebc-4240-899c-ab26f05dea9c Gonzalez, A. (Arantxa)\|\|\|/items/9c64c0f4-66b4-4b51-8593-0e50c091a515 Thum, T. (Thomas)\|\|\|/items/c2b8a6be-55a5-4810-afe7-c5b019ebb02a
author_role	author
author2	Jung, M. (Mira)\|\|\|/items/55431b8b-35ee-4dcf-8e5e-8b08e6e2827c Foinquinos, A. (Ariana)\|\|\|/items/2999aa62-73a3-42b7-99b2-c2e69454aef6 San-José-Enériz, G. (Gorka)\|\|\|/items/362ac8c3-5d50-4383-9fc1-7abbed048387 Beaumont-Ezcurra, F.J. (Francisco Javier)\|\|\|/items/6824d098-1970-4668-9169-8f1f3352e015 Bock, K. (Katharina)\|\|\|/items/bc845b4d-826c-4062-b66b-07dc2b56c3f7 Grote-Levi, L. (Lea)\|\|\|/items/e7838932-cd4e-4617-bb71-e73c81fa34c4 Xiao, K. (Ke)\|\|\|/items/efd36424-9892-4b59-95ac-381ad6f0b49d Bär, C. (Christian)\|\|\|/items/e18d378a-d1b0-49e0-b17c-cbc2446db784 Pfanne, A. (Angelika)\|\|\|/items/58cec70d-6f74-48d8-a22d-cceda444fc50 Just, A. (Annette)\|\|\|/items/94da7ba3-4871-4557-bb7c-a43777891914 Zimmer, K. (Karina)\|\|\|/items/fc6d04ba-cbac-4373-8d36-8d3f9d2c9533 Ngoy, S. (Soeun)\|\|\|/items/b56c93cf-229a-4f54-91b6-41c70fad5b2c Lopez-Salazar, M.B. (María Begoña)\|\|\|/items/153e0e37-14b0-403e-afab-8af00c4edde0 Ravassa-Albéniz, S. (Susana)\|\|\|/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1 Samolovac, S. (Sabine)\|\|\|/items/afb76b87-7740-4b3d-9c34-8051bd6a20c8 Janssen-Peters, H. (Heike)\|\|\|/items/1afa51e2-5698-488c-a15c-4ccdc6378506 Remke, J. (Janet)\|\|\|/items/94a9afeb-8615-4ef2-8fab-5ec4b87e29ab Scherf, K. (Kristian)\|\|\|/items/f11c61fe-a5f7-477d-8ab7-03c42b0fb03d Dangwal, S. (Seema)\|\|\|/items/7551716b-ff32-4d80-819a-c3e21b3f1cd8 Piccoli, M.T. (Maria-Teresa)\|\|\|/items/f16f01e7-db3f-428c-91ec-d74873ca3647 Kleemiss, F. (Felix)\|\|\|/items/e79b7681-1194-4143-9932-7b8842be822d Kreutzer, F.P. (Fabian Philipp)\|\|\|/items/b147d259-b4bb-4888-bca6-2d361089dcb0 Kenneweg, F. (Franziska)\|\|\|/items/25fd4ebb-ce36-4e47-995c-91f2e1b9ed90 Leonardy, J. (Julia)\|\|\|/items/6f6e8618-8901-407b-bdfe-8d26486a0a4f Hobuss, L. (Lisa)\|\|\|/items/9ea2b6f7-fbfc-4d19-a0fa-8cffd8dd33d0 Santer, L. (Laura)\|\|\|/items/a3c367f6-93c7-4ab8-9e2d-1fa08f5f7e30 Do, Q.T. (Quoc-Tuan)\|\|\|/items/8dd0ef69-394b-43d7-a17a-c29c61ce1027 Geffers, R. (Robert)\|\|\|/items/007f5c8f-ce2d-40ff-b6e4-7659912b33ed Braesen, J.H. (Jan Hinrich)\|\|\|/items/b499fca6-9ca9-45c6-8b56-f7531e7c8043 Schmitz, J. (Jessica)\|\|\|/items/ccd4ceeb-611a-4405-8427-1a7a01c1bde3 Brandenberger, C. (Christina)\|\|\|/items/565d2c4a-7fea-4e7e-8aa2-f0332717280d Müller, D.N. (Dominik N.)\|\|\|/items/9bbb7bf5-2c89-40ef-8742-22b5759d022c Wilck, N. (Nicola)\|\|\|/items/2b9af0ea-e805-422b-a411-26aed9607e3c Kaever, V. (Volkhard)\|\|\|/items/5e9e0e4f-1d3f-41db-8815-f8d6ef95d608 Bähre, H. (Heike)\|\|\|/items/b0975de2-400a-4c5f-8aed-aefef4641e9e Batkai, S. (Sandor)\|\|\|/items/a219d6b4-89a4-4f08-bf5f-55816dec3a22 Fiedler, J. (Jan)\|\|\|/items/ef7f7706-d97b-435c-8d15-485034293bea Alexander, K.M. (Kevin M.)\|\|\|/items/ae5ef3ee-e558-46a8-b37f-3832a812e695 Wertheim, B.M. (Bradley M.)\|\|\|/items/c4effae0-40c1-47b8-b218-16cede54c3a2 Fisch, S. (Sudeshna)\|\|\|/items/3086287b-fe51-43d0-8303-c009187a5853 Liao, R. (Ronglih)\|\|\|/items/a9dce0fe-8681-43d5-8dbe-ac02af7531e0 Diez, J. (Javier)\|\|\|/items/adeda0be-cebc-4240-899c-ab26f05dea9c Gonzalez, A. (Arantxa)\|\|\|/items/9c64c0f4-66b4-4b51-8593-0e50c091a515 Thum, T. (Thomas)\|\|\|/items/c2b8a6be-55a5-4810-afe7-c5b019ebb02a
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv	Diastole Fibrosis Hypertension microRNAs
topic	Diastole Fibrosis Hypertension microRNAs
description	BACKGROUND: Myocardial fibrosis is a hallmark of cardiac remodeling and functionally involved in heart failure development, a leading cause of deaths worldwide. Clinically, no therapeutic strategy is available that specifically attenuates maladaptive responses of cardiac fibroblasts, the effector cells of fibrosis in the heart. Therefore, our aim was to develop novel antifibrotic therapeutics based on naturally derived substance library screens for the treatment of cardiac fibrosis. METHODS: Antifibrotic drug candidates were identified by functional screening of 480 chemically diverse natural compounds in primary human cardiac fibroblasts, subsequent validation, and mechanistic in vitro and in vivo studies. Hits were analyzed for dose-dependent inhibition of proliferation of human cardiac fibroblasts, modulation of apoptosis, and extracellular matrix expression. In vitro findings were confirmed in vivo with an angiotensin II–mediated murine model of cardiac fibrosis in both preventive and therapeutic settings, as well as in the Dahl salt-sensitive rat model. To investigate the mechanism underlying the antifibrotic potential of the lead compounds, treatment-dependent changes in the noncoding RNAome in primary human cardiac fibroblasts were analyzed by RNA deep sequencing. RESULTS: High-throughput natural compound library screening identified 15 substances with antiproliferative effects in human cardiac fibroblasts. Using multiple in vitro fibrosis assays and stringent selection algorithms, we identified the steroid bufalin (from Chinese toad venom) and the alkaloid lycorine (from Amaryllidaceae species) to be effective antifibrotic molecules both in vitro and in vivo, leading to improvement in diastolic function in 2 hypertension-dependent rodent models of cardiac fibrosis. Administration at effective doses did not change plasma damage markers or the morphology of kidney and liver, providing the first toxicological safety data. Using next-generation sequencing, we identified the conserved microRNA 671-5p and downstream the antifibrotic selenoprotein P1 as common effectors of the antifibrotic compounds. CONCLUSIONS: We identified the molecules bufalin and lycorine as drug candidates for therapeutic applications in cardiac fibrosis and diastolic dysfunction.
publishDate	2020
dc.date.none.fl_str_mv	2020 2020-01-01 2020 2020-01-01 2023 2023-08-25
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/10171/67169
url	https://hdl.handle.net/10171/67169
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.source.none.fl_str_mv	reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra
instname_str	Universidad de Navarra
reponame_str	Dadun. Depósito Académico Digital de la Universidad de Navarra
collection	Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling	Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic DysfunctionSchimmel, K. (Katharina)\|\|\|/items/db398c60-e014-48da-843a-880afc77498dJung, M. (Mira)\|\|\|/items/55431b8b-35ee-4dcf-8e5e-8b08e6e2827cFoinquinos, A. (Ariana)\|\|\|/items/2999aa62-73a3-42b7-99b2-c2e69454aef6San-José-Enériz, G. (Gorka)\|\|\|/items/362ac8c3-5d50-4383-9fc1-7abbed048387Beaumont-Ezcurra, F.J. (Francisco Javier)\|\|\|/items/6824d098-1970-4668-9169-8f1f3352e015Bock, K. (Katharina)\|\|\|/items/bc845b4d-826c-4062-b66b-07dc2b56c3f7Grote-Levi, L. (Lea)\|\|\|/items/e7838932-cd4e-4617-bb71-e73c81fa34c4Xiao, K. (Ke)\|\|\|/items/efd36424-9892-4b59-95ac-381ad6f0b49dBär, C. (Christian)\|\|\|/items/e18d378a-d1b0-49e0-b17c-cbc2446db784Pfanne, A. (Angelika)\|\|\|/items/58cec70d-6f74-48d8-a22d-cceda444fc50Just, A. (Annette)\|\|\|/items/94da7ba3-4871-4557-bb7c-a43777891914Zimmer, K. (Karina)\|\|\|/items/fc6d04ba-cbac-4373-8d36-8d3f9d2c9533Ngoy, S. (Soeun)\|\|\|/items/b56c93cf-229a-4f54-91b6-41c70fad5b2cLopez-Salazar, M.B. (María Begoña)\|\|\|/items/153e0e37-14b0-403e-afab-8af00c4edde0Ravassa-Albéniz, S. (Susana)\|\|\|/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1Samolovac, S. (Sabine)\|\|\|/items/afb76b87-7740-4b3d-9c34-8051bd6a20c8Janssen-Peters, H. (Heike)\|\|\|/items/1afa51e2-5698-488c-a15c-4ccdc6378506Remke, J. (Janet)\|\|\|/items/94a9afeb-8615-4ef2-8fab-5ec4b87e29abScherf, K. (Kristian)\|\|\|/items/f11c61fe-a5f7-477d-8ab7-03c42b0fb03dDangwal, S. (Seema)\|\|\|/items/7551716b-ff32-4d80-819a-c3e21b3f1cd8Piccoli, M.T. (Maria-Teresa)\|\|\|/items/f16f01e7-db3f-428c-91ec-d74873ca3647Kleemiss, F. (Felix)\|\|\|/items/e79b7681-1194-4143-9932-7b8842be822dKreutzer, F.P. (Fabian Philipp)\|\|\|/items/b147d259-b4bb-4888-bca6-2d361089dcb0Kenneweg, F. (Franziska)\|\|\|/items/25fd4ebb-ce36-4e47-995c-91f2e1b9ed90Leonardy, J. (Julia)\|\|\|/items/6f6e8618-8901-407b-bdfe-8d26486a0a4fHobuss, L. (Lisa)\|\|\|/items/9ea2b6f7-fbfc-4d19-a0fa-8cffd8dd33d0Santer, L. (Laura)\|\|\|/items/a3c367f6-93c7-4ab8-9e2d-1fa08f5f7e30Do, Q.T. (Quoc-Tuan)\|\|\|/items/8dd0ef69-394b-43d7-a17a-c29c61ce1027Geffers, R. (Robert)\|\|\|/items/007f5c8f-ce2d-40ff-b6e4-7659912b33edBraesen, J.H. (Jan Hinrich)\|\|\|/items/b499fca6-9ca9-45c6-8b56-f7531e7c8043Schmitz, J. (Jessica)\|\|\|/items/ccd4ceeb-611a-4405-8427-1a7a01c1bde3Brandenberger, C. (Christina)\|\|\|/items/565d2c4a-7fea-4e7e-8aa2-f0332717280dMüller, D.N. (Dominik N.)\|\|\|/items/9bbb7bf5-2c89-40ef-8742-22b5759d022cWilck, N. (Nicola)\|\|\|/items/2b9af0ea-e805-422b-a411-26aed9607e3cKaever, V. (Volkhard)\|\|\|/items/5e9e0e4f-1d3f-41db-8815-f8d6ef95d608Bähre, H. (Heike)\|\|\|/items/b0975de2-400a-4c5f-8aed-aefef4641e9eBatkai, S. (Sandor)\|\|\|/items/a219d6b4-89a4-4f08-bf5f-55816dec3a22Fiedler, J. (Jan)\|\|\|/items/ef7f7706-d97b-435c-8d15-485034293beaAlexander, K.M. (Kevin M.)\|\|\|/items/ae5ef3ee-e558-46a8-b37f-3832a812e695Wertheim, B.M. (Bradley M.)\|\|\|/items/c4effae0-40c1-47b8-b218-16cede54c3a2Fisch, S. (Sudeshna)\|\|\|/items/3086287b-fe51-43d0-8303-c009187a5853Liao, R. (Ronglih)\|\|\|/items/a9dce0fe-8681-43d5-8dbe-ac02af7531e0Diez, J. (Javier)\|\|\|/items/adeda0be-cebc-4240-899c-ab26f05dea9cGonzalez, A. (Arantxa)\|\|\|/items/9c64c0f4-66b4-4b51-8593-0e50c091a515Thum, T. (Thomas)\|\|\|/items/c2b8a6be-55a5-4810-afe7-c5b019ebb02aDiastoleFibrosisHypertensionmicroRNAsBACKGROUND: Myocardial fibrosis is a hallmark of cardiac remodeling and functionally involved in heart failure development, a leading cause of deaths worldwide. Clinically, no therapeutic strategy is available that specifically attenuates maladaptive responses of cardiac fibroblasts, the effector cells of fibrosis in the heart. Therefore, our aim was to develop novel antifibrotic therapeutics based on naturally derived substance library screens for the treatment of cardiac fibrosis. METHODS: Antifibrotic drug candidates were identified by functional screening of 480 chemically diverse natural compounds in primary human cardiac fibroblasts, subsequent validation, and mechanistic in vitro and in vivo studies. Hits were analyzed for dose-dependent inhibition of proliferation of human cardiac fibroblasts, modulation of apoptosis, and extracellular matrix expression. In vitro findings were confirmed in vivo with an angiotensin II–mediated murine model of cardiac fibrosis in both preventive and therapeutic settings, as well as in the Dahl salt-sensitive rat model. To investigate the mechanism underlying the antifibrotic potential of the lead compounds, treatment-dependent changes in the noncoding RNAome in primary human cardiac fibroblasts were analyzed by RNA deep sequencing. RESULTS: High-throughput natural compound library screening identified 15 substances with antiproliferative effects in human cardiac fibroblasts. Using multiple in vitro fibrosis assays and stringent selection algorithms, we identified the steroid bufalin (from Chinese toad venom) and the alkaloid lycorine (from Amaryllidaceae species) to be effective antifibrotic molecules both in vitro and in vivo, leading to improvement in diastolic function in 2 hypertension-dependent rodent models of cardiac fibrosis. Administration at effective doses did not change plasma damage markers or the morphology of kidney and liver, providing the first toxicological safety data. Using next-generation sequencing, we identified the conserved microRNA 671-5p and downstream the antifibrotic selenoprotein P1 as common effectors of the antifibrotic compounds. CONCLUSIONS: We identified the molecules bufalin and lycorine as drug candidates for therapeutic applications in cardiac fibrosis and diastolic dysfunction.Dadun. Depósito Académico Digital Universidad de Navarra20232023-08-2520202020-01-0120202020-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/67169reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/671692026-06-21T12:47:57Z
score	15,300719

Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction

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