Experimental ischaemic stroke induces transient cardiac atrophy and dysfunction
Abstract Background Stroke can lead to cardiac dysfunction in patients, but the mechanisms underlying the interaction between the injured brain and the heart are poorly understood. The objective of the study is to investigate the effects of experimental murine stroke on cardiac function and molecula...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-02-01
|
| Series: | Journal of Cachexia, Sarcopenia and Muscle |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jcsm.12335 |
| _version_ | 1797204317123379200 |
|---|---|
| author | Roland Veltkamp Stefan Uhlmann Marilena Marinescu Carsten Sticht Daniel Finke Norbert Gretz Herrmann‐Josef Gröne Hugo A. Katus Johannes Backs Lorenz H. Lehmann |
| author_facet | Roland Veltkamp Stefan Uhlmann Marilena Marinescu Carsten Sticht Daniel Finke Norbert Gretz Herrmann‐Josef Gröne Hugo A. Katus Johannes Backs Lorenz H. Lehmann |
| author_sort | Roland Veltkamp |
| collection | DOAJ |
| description | Abstract Background Stroke can lead to cardiac dysfunction in patients, but the mechanisms underlying the interaction between the injured brain and the heart are poorly understood. The objective of the study is to investigate the effects of experimental murine stroke on cardiac function and molecular signalling in the heart. Methods and results Mice were subjected to filament‐induced left middle cerebral artery occlusion for 30 or 60 min or sham surgery and underwent repetitive micro‐echocardiography. Left ventricular contractility was reduced early (24–72 h) but not late (2 months) after brain ischaemia. Cardiac dysfunction was accompanied by a release of high‐sensitive cardiac troponin (hsTNT (ng/ml): d1: 7.0 ± 1.0 vs. 25.0 ± 3.2*; d3: 7.3 ± 1.1 vs. 52.2 ± 16.7*; d14: 5.7 ± 0.8 vs. 5.2 ± 0.3; sham vs. 60 min. MCAO; mean ± SEM; *p < 0.05); reduced heart weight (heart weight/tibia length ratio: d1: 6.9 ± 0.2 vs. 6.4 ± 0.1*; d3: 6.7 ± 0.2 vs. 5.8 ± 0.1*; d14: 6.7 ± 0.2 vs. 6.4 ± 03; sham vs. 60 min. MCAO; mean ± SEM; *p < 0.05); resulting from cardiomyocyte atrophy (cardiomyocyte size: d1: 12.8% ± 0.002**; d3: 13.5% ± 0.002**; 14d: 6.3% ± 0.003*; 60 min. MCAO vs. sham; mean ± SEM; **p < 0.01; *p < 0.05), accompanied by increased atrogin‐1 and the E3 ubiquitin ligase murf‐1. Net norepinephrine but not synthesis was increased, suggesting a reduced norepinephrine release or an increase of norepinephrine re‐uptake, resulting in a functional denervation. Transcriptome analysis in cardiac tissue identified the transcription factor peroxisome proliferator‐activated receptor gamma as a potential mediator of stroke‐induced transcriptional dysregulation involved in cardiac atrophy. Conclusions Stroke induces a complex molecular response in the heart muscle with immediate but transient cardiac atrophy and dysfunction. |
| first_indexed | 2024-04-24T08:33:18Z |
| format | Article |
| id | doaj.art-4ee6e77f3fe14839a1616c6e00904b7a |
| institution | Directory Open Access Journal |
| issn | 2190-5991 2190-6009 |
| language | English |
| last_indexed | 2024-04-24T08:33:18Z |
| publishDate | 2019-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj.art-4ee6e77f3fe14839a1616c6e00904b7a2024-04-16T18:38:30ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092019-02-01101546210.1002/jcsm.12335Experimental ischaemic stroke induces transient cardiac atrophy and dysfunctionRoland Veltkamp0Stefan Uhlmann1Marilena Marinescu2Carsten Sticht3Daniel Finke4Norbert Gretz5Herrmann‐Josef Gröne6Hugo A. Katus7Johannes Backs8Lorenz H. Lehmann9Division of Brain Sciences Imperial College London London UKDepartment of Neurology University Heidelberg Heidelberg GermanyDivision of Brain Sciences Imperial College London London UKMedical Research Center Medical Faculty Mannheim Mannheim GermanyDepartment of Cardiology University of Heidelberg Heidelberg GermanyMedical Research Center Medical Faculty Mannheim Mannheim GermanyDepartment of Cellular and Molecular Pathology German Cancer Research Center Heidelberg GermanyDepartment of Cardiology University of Heidelberg Heidelberg GermanyDepartment of Molecular Cardiology and Epigenetics University of Heidelberg Heidelberg GermanyDepartment of Cardiology University of Heidelberg Heidelberg GermanyAbstract Background Stroke can lead to cardiac dysfunction in patients, but the mechanisms underlying the interaction between the injured brain and the heart are poorly understood. The objective of the study is to investigate the effects of experimental murine stroke on cardiac function and molecular signalling in the heart. Methods and results Mice were subjected to filament‐induced left middle cerebral artery occlusion for 30 or 60 min or sham surgery and underwent repetitive micro‐echocardiography. Left ventricular contractility was reduced early (24–72 h) but not late (2 months) after brain ischaemia. Cardiac dysfunction was accompanied by a release of high‐sensitive cardiac troponin (hsTNT (ng/ml): d1: 7.0 ± 1.0 vs. 25.0 ± 3.2*; d3: 7.3 ± 1.1 vs. 52.2 ± 16.7*; d14: 5.7 ± 0.8 vs. 5.2 ± 0.3; sham vs. 60 min. MCAO; mean ± SEM; *p < 0.05); reduced heart weight (heart weight/tibia length ratio: d1: 6.9 ± 0.2 vs. 6.4 ± 0.1*; d3: 6.7 ± 0.2 vs. 5.8 ± 0.1*; d14: 6.7 ± 0.2 vs. 6.4 ± 03; sham vs. 60 min. MCAO; mean ± SEM; *p < 0.05); resulting from cardiomyocyte atrophy (cardiomyocyte size: d1: 12.8% ± 0.002**; d3: 13.5% ± 0.002**; 14d: 6.3% ± 0.003*; 60 min. MCAO vs. sham; mean ± SEM; **p < 0.01; *p < 0.05), accompanied by increased atrogin‐1 and the E3 ubiquitin ligase murf‐1. Net norepinephrine but not synthesis was increased, suggesting a reduced norepinephrine release or an increase of norepinephrine re‐uptake, resulting in a functional denervation. Transcriptome analysis in cardiac tissue identified the transcription factor peroxisome proliferator‐activated receptor gamma as a potential mediator of stroke‐induced transcriptional dysregulation involved in cardiac atrophy. Conclusions Stroke induces a complex molecular response in the heart muscle with immediate but transient cardiac atrophy and dysfunction.https://doi.org/10.1002/jcsm.12335Ischaemic strokeCardiac dysfunctionAtrophyCardiomyocytesLeft ventricular contractility |
| spellingShingle | Roland Veltkamp Stefan Uhlmann Marilena Marinescu Carsten Sticht Daniel Finke Norbert Gretz Herrmann‐Josef Gröne Hugo A. Katus Johannes Backs Lorenz H. Lehmann Experimental ischaemic stroke induces transient cardiac atrophy and dysfunction Journal of Cachexia, Sarcopenia and Muscle Ischaemic stroke Cardiac dysfunction Atrophy Cardiomyocytes Left ventricular contractility |
| title | Experimental ischaemic stroke induces transient cardiac atrophy and dysfunction |
| title_full | Experimental ischaemic stroke induces transient cardiac atrophy and dysfunction |
| title_fullStr | Experimental ischaemic stroke induces transient cardiac atrophy and dysfunction |
| title_full_unstemmed | Experimental ischaemic stroke induces transient cardiac atrophy and dysfunction |
| title_short | Experimental ischaemic stroke induces transient cardiac atrophy and dysfunction |
| title_sort | experimental ischaemic stroke induces transient cardiac atrophy and dysfunction |
| topic | Ischaemic stroke Cardiac dysfunction Atrophy Cardiomyocytes Left ventricular contractility |
| url | https://doi.org/10.1002/jcsm.12335 |
| work_keys_str_mv | AT rolandveltkamp experimentalischaemicstrokeinducestransientcardiacatrophyanddysfunction AT stefanuhlmann experimentalischaemicstrokeinducestransientcardiacatrophyanddysfunction AT marilenamarinescu experimentalischaemicstrokeinducestransientcardiacatrophyanddysfunction AT carstensticht experimentalischaemicstrokeinducestransientcardiacatrophyanddysfunction AT danielfinke experimentalischaemicstrokeinducestransientcardiacatrophyanddysfunction AT norbertgretz experimentalischaemicstrokeinducestransientcardiacatrophyanddysfunction AT herrmannjosefgrone experimentalischaemicstrokeinducestransientcardiacatrophyanddysfunction AT hugoakatus experimentalischaemicstrokeinducestransientcardiacatrophyanddysfunction AT johannesbacks experimentalischaemicstrokeinducestransientcardiacatrophyanddysfunction AT lorenzhlehmann experimentalischaemicstrokeinducestransientcardiacatrophyanddysfunction |