Cargando…
Development of nonfibrotic left ventricular hypertrophy in an ANG II‐induced chronic ovine hypertension model
Hypertension is a major risk factor for many cardiovascular diseases and leads to subsequent concomitant pathologies such as left ventricular hypertrophy (LVH). Translational approaches using large animals get more important as they allow the use of standard clinical procedures in an experimental se...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027340/ https://www.ncbi.nlm.nih.gov/pubmed/27613823 http://dx.doi.org/10.14814/phy2.12897 |
_version_ | 1782454226818957312 |
---|---|
author | Klatt, Niklas Scherschel, Katharina Schad, Claudia Lau, Denise Reitmeier, Aline Kuklik, Pawel Muellerleile, Kai Yamamura, Jin Zeller, Tanja Steven, Daniel Baldus, Stephan Schäffer, Benjamin Jungen, Christiane Eickholt, Christian Wassilew, Katharina Schwedhelm, Edzard Willems, Stephan Meyer, Christian |
author_facet | Klatt, Niklas Scherschel, Katharina Schad, Claudia Lau, Denise Reitmeier, Aline Kuklik, Pawel Muellerleile, Kai Yamamura, Jin Zeller, Tanja Steven, Daniel Baldus, Stephan Schäffer, Benjamin Jungen, Christiane Eickholt, Christian Wassilew, Katharina Schwedhelm, Edzard Willems, Stephan Meyer, Christian |
author_sort | Klatt, Niklas |
collection | PubMed |
description | Hypertension is a major risk factor for many cardiovascular diseases and leads to subsequent concomitant pathologies such as left ventricular hypertrophy (LVH). Translational approaches using large animals get more important as they allow the use of standard clinical procedures in an experimental setting. Therefore, the aim of this study was to establish a minimally invasive ovine hypertension model using chronic angiotensin II (ANG II) treatment and to characterize its effects on cardiac remodeling after 8 weeks. Sheep were implanted with osmotic minipumps filled with either vehicle control (n = 7) or ANG II (n = 9) for 8 weeks. Mean arterial blood pressure in the ANG II‐treated group increased from 87.4 ± 5.3 to 111.8 ± 6.9 mmHg (P = 0.00013). Cardiovascular magnetic resonance imaging showed an increase in left ventricular mass from 112 ± 12.6 g to 131 ± 18.7 g after 7 weeks (P = 0.0017). This was confirmed by postmortem measurement of left ventricular wall thickness which was higher in ANG II‐treated animals compared to the control group (18 ± 4 mm vs. 13 ± 2 mm, respectively, P = 0.002). However, ANG II‐treated sheep did not reveal any signs of fibrosis or inflammatory infiltrates as defined by picrosirius red and H&E staining on myocardial full thickness paraffin sections of both atria and ventricles. Measurements of plasma high‐sensitivity C‐reactive protein and urinary 8‐iso‐prostaglandin F(2α) were inconspicuous in all animals. Furthermore, multielectrode surface mapping of the heart did not show any differences in epicardial conduction velocity and heterogeneity. These data demonstrate that chronic ANG II treatment using osmotic minipumps presents a reliable, minimally invasive approach to establish hypertension and nonfibrotic LVH in sheep. |
format | Online Article Text |
id | pubmed-5027340 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-50273402017-03-07 Development of nonfibrotic left ventricular hypertrophy in an ANG II‐induced chronic ovine hypertension model Klatt, Niklas Scherschel, Katharina Schad, Claudia Lau, Denise Reitmeier, Aline Kuklik, Pawel Muellerleile, Kai Yamamura, Jin Zeller, Tanja Steven, Daniel Baldus, Stephan Schäffer, Benjamin Jungen, Christiane Eickholt, Christian Wassilew, Katharina Schwedhelm, Edzard Willems, Stephan Meyer, Christian Physiol Rep Original Research Hypertension is a major risk factor for many cardiovascular diseases and leads to subsequent concomitant pathologies such as left ventricular hypertrophy (LVH). Translational approaches using large animals get more important as they allow the use of standard clinical procedures in an experimental setting. Therefore, the aim of this study was to establish a minimally invasive ovine hypertension model using chronic angiotensin II (ANG II) treatment and to characterize its effects on cardiac remodeling after 8 weeks. Sheep were implanted with osmotic minipumps filled with either vehicle control (n = 7) or ANG II (n = 9) for 8 weeks. Mean arterial blood pressure in the ANG II‐treated group increased from 87.4 ± 5.3 to 111.8 ± 6.9 mmHg (P = 0.00013). Cardiovascular magnetic resonance imaging showed an increase in left ventricular mass from 112 ± 12.6 g to 131 ± 18.7 g after 7 weeks (P = 0.0017). This was confirmed by postmortem measurement of left ventricular wall thickness which was higher in ANG II‐treated animals compared to the control group (18 ± 4 mm vs. 13 ± 2 mm, respectively, P = 0.002). However, ANG II‐treated sheep did not reveal any signs of fibrosis or inflammatory infiltrates as defined by picrosirius red and H&E staining on myocardial full thickness paraffin sections of both atria and ventricles. Measurements of plasma high‐sensitivity C‐reactive protein and urinary 8‐iso‐prostaglandin F(2α) were inconspicuous in all animals. Furthermore, multielectrode surface mapping of the heart did not show any differences in epicardial conduction velocity and heterogeneity. These data demonstrate that chronic ANG II treatment using osmotic minipumps presents a reliable, minimally invasive approach to establish hypertension and nonfibrotic LVH in sheep. John Wiley and Sons Inc. 2016-09-13 /pmc/articles/PMC5027340/ /pubmed/27613823 http://dx.doi.org/10.14814/phy2.12897 Text en © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Klatt, Niklas Scherschel, Katharina Schad, Claudia Lau, Denise Reitmeier, Aline Kuklik, Pawel Muellerleile, Kai Yamamura, Jin Zeller, Tanja Steven, Daniel Baldus, Stephan Schäffer, Benjamin Jungen, Christiane Eickholt, Christian Wassilew, Katharina Schwedhelm, Edzard Willems, Stephan Meyer, Christian Development of nonfibrotic left ventricular hypertrophy in an ANG II‐induced chronic ovine hypertension model |
title | Development of nonfibrotic left ventricular hypertrophy in an ANG II‐induced chronic ovine hypertension model |
title_full | Development of nonfibrotic left ventricular hypertrophy in an ANG II‐induced chronic ovine hypertension model |
title_fullStr | Development of nonfibrotic left ventricular hypertrophy in an ANG II‐induced chronic ovine hypertension model |
title_full_unstemmed | Development of nonfibrotic left ventricular hypertrophy in an ANG II‐induced chronic ovine hypertension model |
title_short | Development of nonfibrotic left ventricular hypertrophy in an ANG II‐induced chronic ovine hypertension model |
title_sort | development of nonfibrotic left ventricular hypertrophy in an ang ii‐induced chronic ovine hypertension model |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027340/ https://www.ncbi.nlm.nih.gov/pubmed/27613823 http://dx.doi.org/10.14814/phy2.12897 |
work_keys_str_mv | AT klattniklas developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT scherschelkatharina developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT schadclaudia developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT laudenise developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT reitmeieraline developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT kuklikpawel developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT muellerleilekai developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT yamamurajin developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT zellertanja developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT stevendaniel developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT baldusstephan developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT schafferbenjamin developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT jungenchristiane developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT eickholtchristian developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT wassilewkatharina developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT schwedhelmedzard developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT willemsstephan developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel AT meyerchristian developmentofnonfibroticleftventricularhypertrophyinanangiiinducedchronicovinehypertensionmodel |