Hypoxia Attenuates Pressure Overload‐Induced Heart Failure
Background Alveolar hypoxia is protective in the context of cardiovascular and ischemic heart disease; however, the underlying mechanisms are incompletely understood. The present study sought to test the hypothesis that hypoxia is cardioprotective in left ventricular pressure overload (LVPO)–induced...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.123.033553 |
| _version_ | 1797296313030672384 |
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| author | Natali Froese Malgorzata Szaroszyk Paolo Galuppo Joseph R. Visker Christopher Werlein Mortimer Korf‐Klingebiel Dominik Berliner Marc R. Reboll Rana Hamouche Simona Gegel Yong Wang Winfried Hofmann Ming Tang Robert Geffers Adam R. Wende Mark P. Kühnel Danny D. Jonigk Georg Hansmann Kai C. Wollert E. Dale Abel Stavros G. Drakos Johann Bauersachs Christian Riehle |
| author_facet | Natali Froese Malgorzata Szaroszyk Paolo Galuppo Joseph R. Visker Christopher Werlein Mortimer Korf‐Klingebiel Dominik Berliner Marc R. Reboll Rana Hamouche Simona Gegel Yong Wang Winfried Hofmann Ming Tang Robert Geffers Adam R. Wende Mark P. Kühnel Danny D. Jonigk Georg Hansmann Kai C. Wollert E. Dale Abel Stavros G. Drakos Johann Bauersachs Christian Riehle |
| author_sort | Natali Froese |
| collection | DOAJ |
| description | Background Alveolar hypoxia is protective in the context of cardiovascular and ischemic heart disease; however, the underlying mechanisms are incompletely understood. The present study sought to test the hypothesis that hypoxia is cardioprotective in left ventricular pressure overload (LVPO)–induced heart failure. We furthermore aimed to test that overlapping mechanisms promote cardiac recovery in heart failure patients following left ventricular assist device‐mediated mechanical unloading and circulatory support. Methods and Results We established a novel murine model of combined chronic alveolar hypoxia and LVPO following transverse aortic constriction (HxTAC). The HxTAC model is resistant to cardiac hypertrophy and the development of heart failure. The cardioprotective mechanisms identified in our HxTAC model include increased activation of HIF (hypoxia‐inducible factor)‐1α–mediated angiogenesis, attenuated induction of genes associated with pathological remodeling, and preserved metabolic gene expression as identified by RNA sequencing. Furthermore, LVPO decreased Tbx5 and increased Hsd11b1 mRNA expression under normoxic conditions, which was attenuated under hypoxic conditions and may induce additional hypoxia‐mediated cardioprotective effects. Analysis of samples from patients with advanced heart failure that demonstrated left ventricular assist device–mediated myocardial recovery revealed a similar expression pattern for TBX5 and HSD11B1 as observed in HxTAC hearts. Conclusions Hypoxia attenuates LVPO‐induced heart failure. Cardioprotective pathways identified in the HxTAC model might also contribute to cardiac recovery following left ventricular assist device support. These data highlight the potential of our novel HxTAC model to identify hypoxia‐mediated cardioprotective mechanisms and therapeutic targets that attenuate LVPO‐induced heart failure and mediate cardiac recovery following mechanical circulatory support. |
| first_indexed | 2024-03-07T22:01:47Z |
| format | Article |
| id | doaj.art-faab23b5566643d4bb708c9cafa2f8de |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-07T22:01:47Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-faab23b5566643d4bb708c9cafa2f8de2024-02-24T04:06:35ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-02-0113310.1161/JAHA.123.033553Hypoxia Attenuates Pressure Overload‐Induced Heart FailureNatali Froese0Malgorzata Szaroszyk1Paolo Galuppo2Joseph R. Visker3Christopher Werlein4Mortimer Korf‐Klingebiel5Dominik Berliner6Marc R. Reboll7Rana Hamouche8Simona Gegel9Yong Wang10Winfried Hofmann11Ming Tang12Robert Geffers13Adam R. Wende14Mark P. Kühnel15Danny D. Jonigk16Georg Hansmann17Kai C. Wollert18E. Dale Abel19Stavros G. Drakos20Johann Bauersachs21Christian Riehle22Department of Cardiology and Angiology Hannover Medical School Hannover GermanyDepartment of Cardiology and Angiology Hannover Medical School Hannover GermanyDepartment of Cardiology and Angiology Hannover Medical School Hannover GermanyNora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI) and Division of Cardiovascular Medicine University of Utah School of Medicine Salt Lake City UT USAInstitute of Pathology Hannover Medical School Hannover GermanyDepartment of Cardiology and Angiology Hannover Medical School Hannover GermanyDepartment of Cardiology and Angiology Hannover Medical School Hannover GermanyDepartment of Cardiology and Angiology Hannover Medical School Hannover GermanyNora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI) and Division of Cardiovascular Medicine University of Utah School of Medicine Salt Lake City UT USADepartment of Cardiology and Angiology Hannover Medical School Hannover GermanyDepartment of Cardiology and Angiology Hannover Medical School Hannover GermanyDepartment of Human Genetics Hannover Medical School Hannover GermanyDepartment of Human Genetics Hannover Medical School Hannover GermanyHelmholtz Center for Infection Research Research Group Genome Analytics Braunschweig GermanyDivision of Molecular and Cellular Pathology, Department of Pathology University of Alabama at Birmingham Birmingham AL USAInstitute of Pathology Hannover Medical School Hannover GermanyInstitute of Pathology Hannover Medical School Hannover GermanyDepartment of Pediatric Cardiology and Critical Care Hannover Medical School Hannover GermanyDepartment of Cardiology and Angiology Hannover Medical School Hannover GermanyDepartment of Medicine David Geffen School of Medicine and UCLA Health Los Angeles CA USANora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI) and Division of Cardiovascular Medicine University of Utah School of Medicine Salt Lake City UT USADepartment of Cardiology and Angiology Hannover Medical School Hannover GermanyDepartment of Cardiology and Angiology Hannover Medical School Hannover GermanyBackground Alveolar hypoxia is protective in the context of cardiovascular and ischemic heart disease; however, the underlying mechanisms are incompletely understood. The present study sought to test the hypothesis that hypoxia is cardioprotective in left ventricular pressure overload (LVPO)–induced heart failure. We furthermore aimed to test that overlapping mechanisms promote cardiac recovery in heart failure patients following left ventricular assist device‐mediated mechanical unloading and circulatory support. Methods and Results We established a novel murine model of combined chronic alveolar hypoxia and LVPO following transverse aortic constriction (HxTAC). The HxTAC model is resistant to cardiac hypertrophy and the development of heart failure. The cardioprotective mechanisms identified in our HxTAC model include increased activation of HIF (hypoxia‐inducible factor)‐1α–mediated angiogenesis, attenuated induction of genes associated with pathological remodeling, and preserved metabolic gene expression as identified by RNA sequencing. Furthermore, LVPO decreased Tbx5 and increased Hsd11b1 mRNA expression under normoxic conditions, which was attenuated under hypoxic conditions and may induce additional hypoxia‐mediated cardioprotective effects. Analysis of samples from patients with advanced heart failure that demonstrated left ventricular assist device–mediated myocardial recovery revealed a similar expression pattern for TBX5 and HSD11B1 as observed in HxTAC hearts. Conclusions Hypoxia attenuates LVPO‐induced heart failure. Cardioprotective pathways identified in the HxTAC model might also contribute to cardiac recovery following left ventricular assist device support. These data highlight the potential of our novel HxTAC model to identify hypoxia‐mediated cardioprotective mechanisms and therapeutic targets that attenuate LVPO‐induced heart failure and mediate cardiac recovery following mechanical circulatory support.https://www.ahajournals.org/doi/10.1161/JAHA.123.033553cardiac hypertrophycardiac remodelinghypoxialeft ventricular assist devicepressure overload |
| spellingShingle | Natali Froese Malgorzata Szaroszyk Paolo Galuppo Joseph R. Visker Christopher Werlein Mortimer Korf‐Klingebiel Dominik Berliner Marc R. Reboll Rana Hamouche Simona Gegel Yong Wang Winfried Hofmann Ming Tang Robert Geffers Adam R. Wende Mark P. Kühnel Danny D. Jonigk Georg Hansmann Kai C. Wollert E. Dale Abel Stavros G. Drakos Johann Bauersachs Christian Riehle Hypoxia Attenuates Pressure Overload‐Induced Heart Failure Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease cardiac hypertrophy cardiac remodeling hypoxia left ventricular assist device pressure overload |
| title | Hypoxia Attenuates Pressure Overload‐Induced Heart Failure |
| title_full | Hypoxia Attenuates Pressure Overload‐Induced Heart Failure |
| title_fullStr | Hypoxia Attenuates Pressure Overload‐Induced Heart Failure |
| title_full_unstemmed | Hypoxia Attenuates Pressure Overload‐Induced Heart Failure |
| title_short | Hypoxia Attenuates Pressure Overload‐Induced Heart Failure |
| title_sort | hypoxia attenuates pressure overload induced heart failure |
| topic | cardiac hypertrophy cardiac remodeling hypoxia left ventricular assist device pressure overload |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.033553 |
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