1,8-Cineole ameliorates right ventricle dysfunction associated with pulmonary arterial hypertension by restoring connexin43 and mitochondrial homeostasis
For the first time, the present study unravels a cardiospecific therapeutic approach for Pulmonary Arterial Hypertension (PAH), a disease with a very poor prognosis and high mortality rates due to right ventricle (RV) dysfunction. We first established a new in vitro model of high-pressure-induced hy...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661822000962 |
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| author | Jorge M. Alves-Silva Mónica Zuzarte Carla Marques Sofia Viana Inês Preguiça Rui Baptista Cátia Ferreira Carlos Cavaleiro Neuza Domingues Vilma A. Sardão Paulo J. Oliveira Flávio Reis Lígia Salgueiro Henrique Girão |
| author_facet | Jorge M. Alves-Silva Mónica Zuzarte Carla Marques Sofia Viana Inês Preguiça Rui Baptista Cátia Ferreira Carlos Cavaleiro Neuza Domingues Vilma A. Sardão Paulo J. Oliveira Flávio Reis Lígia Salgueiro Henrique Girão |
| author_sort | Jorge M. Alves-Silva |
| collection | DOAJ |
| description | For the first time, the present study unravels a cardiospecific therapeutic approach for Pulmonary Arterial Hypertension (PAH), a disease with a very poor prognosis and high mortality rates due to right ventricle (RV) dysfunction. We first established a new in vitro model of high-pressure-induced hypertrophy that closely resembles heart defects associated with PAH and validated our in vitro findings on a preclinical in vivo model of monocrotaline (MCT)-induced PAH. Our results showed the in vitro antihypertrophic effect of 1,8-cineole, a monoterpene widely found in several essential oils. Also, a decrease in RV hypertrophy and fibrosis, and an improvement in heart function in vivo was observed, when 1,8-cineole was applied topically. Furthermore, 1,8-cineole restored gap junction protein connexin43 distribution at the intercalated disks and mitochondrial functionality, suggesting it may act by preserving cardiac cell-to-cell communication and bioenergetics. Overall, our results point out a promising therapeutic compound that can be easily applied topically, thus paving the way for the development of effective cardiac-specific therapies to greatly improve PAH outcomes. |
| first_indexed | 2024-03-08T17:07:18Z |
| format | Article |
| id | doaj.art-cef45c65a6144c238f9f9a498ad92b9e |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2024-03-08T17:07:18Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj.art-cef45c65a6144c238f9f9a498ad92b9e2024-01-04T04:36:34ZengElsevierPharmacological Research1096-11862022-06-011801061511,8-Cineole ameliorates right ventricle dysfunction associated with pulmonary arterial hypertension by restoring connexin43 and mitochondrial homeostasisJorge M. Alves-Silva0Mónica Zuzarte1Carla Marques2Sofia Viana3Inês Preguiça4Rui Baptista5Cátia Ferreira6Carlos Cavaleiro7Neuza Domingues8Vilma A. Sardão9Paulo J. Oliveira10Flávio Reis11Lígia Salgueiro12Henrique Girão13Univ Coimbra, Faculty of Pharmacy, Coimbra, Portugal; Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Clinical Academic Centre of Coimbra (CACC), Coimbra, PortugalUniv Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Clinical Academic Centre of Coimbra (CACC), Coimbra, Portugal; Correspondence to: Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Health Sciences Campus, Azinhaga Santa Comba, Celas, 3000-548 Coimbra, Portugal.Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Clinical Academic Centre of Coimbra (CACC), Coimbra, PortugalUniv Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Clinical Academic Centre of Coimbra (CACC), Coimbra, Portugal; Univ Coimbra, Institute of Pharmacology & Experimental Therapeutics, Faculty of Medicine, Coimbra, Portugal; Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Pharmacy, Coimbra, PortugalUniv Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Clinical Academic Centre of Coimbra (CACC), Coimbra, Portugal; Univ Coimbra, Institute of Pharmacology & Experimental Therapeutics, Faculty of Medicine, Coimbra, PortugalUniv Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Clinical Academic Centre of Coimbra (CACC), Coimbra, Portugal; Cardiology Department, Hospital Centre of Entre Douro and Vouga, Santa Maria da Feira, PortugalCardiology Department, Coimbra Hospital and University Centre, Coimbra, PortugalUniv Coimbra, Faculty of Pharmacy, Coimbra, Portugal; Univ Coimbra, Chemical Process Engineering and Forest Products Research Centre (CIEPQPF), Department of Chemical Engineering, Faculty of Sciences and Technology, Coimbra, PortugalUniv Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Clinical Academic Centre of Coimbra (CACC), Coimbra, PortugalUniv Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Univ Coimbra, Center for Neuroscience and Cell Biology (CNC), Coimbra, Portugal; Univ Coimbra, Faculty of Sport Science and Physical Education, Coimbra, PortugalUniv Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Univ Coimbra, Center for Neuroscience and Cell Biology (CNC), Coimbra, PortugalUniv Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Clinical Academic Centre of Coimbra (CACC), Coimbra, Portugal; Univ Coimbra, Institute of Pharmacology & Experimental Therapeutics, Faculty of Medicine, Coimbra, PortugalUniv Coimbra, Faculty of Pharmacy, Coimbra, Portugal; Univ Coimbra, Chemical Process Engineering and Forest Products Research Centre (CIEPQPF), Department of Chemical Engineering, Faculty of Sciences and Technology, Coimbra, PortugalUniv Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Clinical Academic Centre of Coimbra (CACC), Coimbra, PortugalFor the first time, the present study unravels a cardiospecific therapeutic approach for Pulmonary Arterial Hypertension (PAH), a disease with a very poor prognosis and high mortality rates due to right ventricle (RV) dysfunction. We first established a new in vitro model of high-pressure-induced hypertrophy that closely resembles heart defects associated with PAH and validated our in vitro findings on a preclinical in vivo model of monocrotaline (MCT)-induced PAH. Our results showed the in vitro antihypertrophic effect of 1,8-cineole, a monoterpene widely found in several essential oils. Also, a decrease in RV hypertrophy and fibrosis, and an improvement in heart function in vivo was observed, when 1,8-cineole was applied topically. Furthermore, 1,8-cineole restored gap junction protein connexin43 distribution at the intercalated disks and mitochondrial functionality, suggesting it may act by preserving cardiac cell-to-cell communication and bioenergetics. Overall, our results point out a promising therapeutic compound that can be easily applied topically, thus paving the way for the development of effective cardiac-specific therapies to greatly improve PAH outcomes.http://www.sciencedirect.com/science/article/pii/S10436618220009621,8-CineoleConnexin43FibrosisHypertrophyRight ventricleMitophagy |
| spellingShingle | Jorge M. Alves-Silva Mónica Zuzarte Carla Marques Sofia Viana Inês Preguiça Rui Baptista Cátia Ferreira Carlos Cavaleiro Neuza Domingues Vilma A. Sardão Paulo J. Oliveira Flávio Reis Lígia Salgueiro Henrique Girão 1,8-Cineole ameliorates right ventricle dysfunction associated with pulmonary arterial hypertension by restoring connexin43 and mitochondrial homeostasis Pharmacological Research 1,8-Cineole Connexin43 Fibrosis Hypertrophy Right ventricle Mitophagy |
| title | 1,8-Cineole ameliorates right ventricle dysfunction associated with pulmonary arterial hypertension by restoring connexin43 and mitochondrial homeostasis |
| title_full | 1,8-Cineole ameliorates right ventricle dysfunction associated with pulmonary arterial hypertension by restoring connexin43 and mitochondrial homeostasis |
| title_fullStr | 1,8-Cineole ameliorates right ventricle dysfunction associated with pulmonary arterial hypertension by restoring connexin43 and mitochondrial homeostasis |
| title_full_unstemmed | 1,8-Cineole ameliorates right ventricle dysfunction associated with pulmonary arterial hypertension by restoring connexin43 and mitochondrial homeostasis |
| title_short | 1,8-Cineole ameliorates right ventricle dysfunction associated with pulmonary arterial hypertension by restoring connexin43 and mitochondrial homeostasis |
| title_sort | 1 8 cineole ameliorates right ventricle dysfunction associated with pulmonary arterial hypertension by restoring connexin43 and mitochondrial homeostasis |
| topic | 1,8-Cineole Connexin43 Fibrosis Hypertrophy Right ventricle Mitophagy |
| url | http://www.sciencedirect.com/science/article/pii/S1043661822000962 |
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