Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension
Abstract Background Meaningful translational large animal models for cardiac diseases are indispensable for studying disease mechanisms, development of novel therapeutic strategies, and evaluation of potential drugs. Methods For induction of heart failure, cardiac hypertrophy and fibrosis, a bare me...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-10-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-017-1299-0 |
| _version_ | 1819320007009501184 |
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| author | Mariann Gyöngyösi Noemi Pavo Dominika Lukovic Katrin Zlabinger Andreas Spannbauer Denise Traxler Georg Goliasch Ljubica Mandic Jutta Bergler-Klein Alfred Gugerell Andras Jakab Zsuzsanna Szankai Levente Toth Rita Garamvölgyi Gerald Maurer Frederic Jaisser Faiez Zannad Thomas Thum Sándor Bátkai Johannes Winkler |
| author_facet | Mariann Gyöngyösi Noemi Pavo Dominika Lukovic Katrin Zlabinger Andreas Spannbauer Denise Traxler Georg Goliasch Ljubica Mandic Jutta Bergler-Klein Alfred Gugerell Andras Jakab Zsuzsanna Szankai Levente Toth Rita Garamvölgyi Gerald Maurer Frederic Jaisser Faiez Zannad Thomas Thum Sándor Bátkai Johannes Winkler |
| author_sort | Mariann Gyöngyösi |
| collection | DOAJ |
| description | Abstract Background Meaningful translational large animal models for cardiac diseases are indispensable for studying disease mechanisms, development of novel therapeutic strategies, and evaluation of potential drugs. Methods For induction of heart failure, cardiac hypertrophy and fibrosis, a bare metal stent was implanted in the descending aorta of growing pigs (n = 7), inducing pressure stress on the left ventricle (group HYPI). The constant stent size in growing pigs resulted in antegrade partial obstruction of the aortic flow with a gradual increase in afterload. Five pigs with sham intervention served as control. Serial haemodynamic, pressure–volume loop measurements and transthoracic echocardiography (TTE) were performed to detect developing pressure overload of the LV and cardiac MRI with late enhancement for measuring LV and RV mass and ejection fraction. Results At 5-month follow-up, CT and contrast aortography, and intraluminal echocardiography confirmed aortic isthmus stenosis with a mean trans-stenotic gradient of 64 ± 13.9 mmHg. Invasive haemodynamic measurements revealed a secondary increase in pulmonary artery pressure (44.6 ± 5.1 vs 25.9 ± 6.2 mmHg, HYPI vs control, p < 0.05). TTE and ex vivo analyses confirmed severe concentric LV hypertrophy (mean circumferential wall thickness, 19.4 ± 3.1, n = 7 vs 11.4 ± 1.0 mm, n = 5, HYPI vs controls, p < 0.05). The LV and RV mass increased significantly, paralleled by increased isovolumic relaxation constant (tau). Histological analyses confirmed substantial fibrosis and myocyte hypertrophy in both LV and RV. Expressions of ANP, BNP, and miRNA-29a were up-regulated, while SERCA2a and miRNA-1 were down-regulated. Plasma NGAL levels increased gradually, while the elevation of NT-proBNP was detected only at the 5-month FUP. Conclusion These data prove that percutaneous artificial aortic stenosis in pigs is useful for inducing clinically relevant progredient heart failure based on myocardial hypertrophy and fibrosis. |
| first_indexed | 2024-12-24T11:12:43Z |
| format | Article |
| id | doaj.art-e9011016638048b8a2c017f7acbe8f45 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-24T11:12:43Z |
| publishDate | 2017-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-e9011016638048b8a2c017f7acbe8f452022-12-21T16:58:29ZengBMCJournal of Translational Medicine1479-58762017-10-0115111510.1186/s12967-017-1299-0Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertensionMariann Gyöngyösi0Noemi Pavo1Dominika Lukovic2Katrin Zlabinger3Andreas Spannbauer4Denise Traxler5Georg Goliasch6Ljubica Mandic7Jutta Bergler-Klein8Alfred Gugerell9Andras Jakab10Zsuzsanna Szankai11Levente Toth12Rita Garamvölgyi13Gerald Maurer14Frederic Jaisser15Faiez Zannad16Thomas Thum17Sándor Bátkai18Johannes Winkler19Department of Cardiology, Medical University of ViennaDepartment of Cardiology, Medical University of ViennaDepartment of Cardiology, Medical University of ViennaDepartment of Cardiology, Medical University of ViennaDepartment of Cardiology, Medical University of ViennaDepartment of Cardiology, Medical University of ViennaDepartment of Cardiology, Medical University of ViennaDepartment of Cardiology, Medical University of ViennaDepartment of Cardiology, Medical University of ViennaDepartment of Cardiology, Medical University of ViennaDepartment of Cardiology, Medical University of ViennaDepartment of Cardiology, Medical University of ViennaInstitute of Diagnostic Imaging and Radiation Oncology, University of KaposvarInstitute of Diagnostic Imaging and Radiation Oncology, University of KaposvarDepartment of Cardiology, Medical University of ViennaINSERM, UMRS 1138, Team 1, Centre de Recherche des Cordeliers, Pierre et Marie Curie University, Paris Descartes UniversityCentre d’Investigation Clinique Inserm, CHU, Université de LorraineInstitute for Molecular and Translational Therapeutic Strategies (IMTTS)Institute for Molecular and Translational Therapeutic Strategies (IMTTS)Department of Cardiology, Medical University of ViennaAbstract Background Meaningful translational large animal models for cardiac diseases are indispensable for studying disease mechanisms, development of novel therapeutic strategies, and evaluation of potential drugs. Methods For induction of heart failure, cardiac hypertrophy and fibrosis, a bare metal stent was implanted in the descending aorta of growing pigs (n = 7), inducing pressure stress on the left ventricle (group HYPI). The constant stent size in growing pigs resulted in antegrade partial obstruction of the aortic flow with a gradual increase in afterload. Five pigs with sham intervention served as control. Serial haemodynamic, pressure–volume loop measurements and transthoracic echocardiography (TTE) were performed to detect developing pressure overload of the LV and cardiac MRI with late enhancement for measuring LV and RV mass and ejection fraction. Results At 5-month follow-up, CT and contrast aortography, and intraluminal echocardiography confirmed aortic isthmus stenosis with a mean trans-stenotic gradient of 64 ± 13.9 mmHg. Invasive haemodynamic measurements revealed a secondary increase in pulmonary artery pressure (44.6 ± 5.1 vs 25.9 ± 6.2 mmHg, HYPI vs control, p < 0.05). TTE and ex vivo analyses confirmed severe concentric LV hypertrophy (mean circumferential wall thickness, 19.4 ± 3.1, n = 7 vs 11.4 ± 1.0 mm, n = 5, HYPI vs controls, p < 0.05). The LV and RV mass increased significantly, paralleled by increased isovolumic relaxation constant (tau). Histological analyses confirmed substantial fibrosis and myocyte hypertrophy in both LV and RV. Expressions of ANP, BNP, and miRNA-29a were up-regulated, while SERCA2a and miRNA-1 were down-regulated. Plasma NGAL levels increased gradually, while the elevation of NT-proBNP was detected only at the 5-month FUP. Conclusion These data prove that percutaneous artificial aortic stenosis in pigs is useful for inducing clinically relevant progredient heart failure based on myocardial hypertrophy and fibrosis.http://link.springer.com/article/10.1186/s12967-017-1299-0Cardiac hypertrophyPET-MRI imagingAortic isthmus stenosisTranslational large animal modelGene expression |
| spellingShingle | Mariann Gyöngyösi Noemi Pavo Dominika Lukovic Katrin Zlabinger Andreas Spannbauer Denise Traxler Georg Goliasch Ljubica Mandic Jutta Bergler-Klein Alfred Gugerell Andras Jakab Zsuzsanna Szankai Levente Toth Rita Garamvölgyi Gerald Maurer Frederic Jaisser Faiez Zannad Thomas Thum Sándor Bátkai Johannes Winkler Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension Journal of Translational Medicine Cardiac hypertrophy PET-MRI imaging Aortic isthmus stenosis Translational large animal model Gene expression |
| title | Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension |
| title_full | Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension |
| title_fullStr | Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension |
| title_full_unstemmed | Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension |
| title_short | Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension |
| title_sort | porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension |
| topic | Cardiac hypertrophy PET-MRI imaging Aortic isthmus stenosis Translational large animal model Gene expression |
| url | http://link.springer.com/article/10.1186/s12967-017-1299-0 |
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