Different activation of MAPKs and Akt/GSK3β after preload vs. afterload elevation
Abstract Aims Pressure overload (PO) and volume overload (VO) lead to concentric or eccentric hypertrophy. Previously, we could show that activation of signalling cascades differ in in vivo mouse models. Activation of these signal cascades could either be induced by intrinsic load sensing or neuro‐e...
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Wiley
2022-06-01
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| Series: | ESC Heart Failure |
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| Online Access: | https://doi.org/10.1002/ehf2.13877 |
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| author | Nico Hartmann Lena Preuß Belal A. Mohamed Moritz Schnelle Andre Renner Gerd Hasenfuß Karl Toischer |
| author_facet | Nico Hartmann Lena Preuß Belal A. Mohamed Moritz Schnelle Andre Renner Gerd Hasenfuß Karl Toischer |
| author_sort | Nico Hartmann |
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| description | Abstract Aims Pressure overload (PO) and volume overload (VO) lead to concentric or eccentric hypertrophy. Previously, we could show that activation of signalling cascades differ in in vivo mouse models. Activation of these signal cascades could either be induced by intrinsic load sensing or neuro‐endocrine substances like catecholamines or the renin‐angiotensin‐aldosterone system. Methods and results We therefore analysed the activation of classical cardiac signal pathways [mitogen‐activated protein kinases (MAPKs) (ERK, p38, and JNK) and Akt‐GSK3β] in in vitro of mechanical overload (ejecting heart model, rabbit and human isolated muscle strips). Selective elevation of preload in vitro increased AKT and GSK3β phosphorylation after 15 min in isolated rabbit muscles strips (AKT 49%, GSK3β 26%, P < 0.05) and in mouse ejecting hearts (AKT 51%, GSK49%, P < 0.05), whereas phosphorylation of MAPKs was not influenced by increased preload. Selective elevation of afterload revealed an increase in ERK phosphorylation in the ejecting heart (43%, P < 0.05), but not in AKT, GSK3β, and the other MAPKs. Elevation of preload and afterload in the ejecting heart induced a significant phosphorylation of ERK (95%, P < 0.001) and showed a moderate increased AKT (P = 0.14) and GSK3β (P = 0.21) phosphorylation, which did not reach significance. Preload and afterload elevation in muscles strips from human failing hearts showed neither AKT nor ERK phosphorylation changes. Conclusions Our data show that preload activates the AKT–GSK3β and afterload the ERK pathway in vitro, indicating an intrinsic mechanism independent of endocrine signalling. |
| format | Article |
| id | doaj-art-b004ae20d1ac401b9f11c9159715a25a |
| institution | Kabale University |
| issn | 2055-5822 |
| language | English |
| publishDate | 2022-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj-art-b004ae20d1ac401b9f11c9159715a25a2025-02-05T05:22:10ZengWileyESC Heart Failure2055-58222022-06-01931823183110.1002/ehf2.13877Different activation of MAPKs and Akt/GSK3β after preload vs. afterload elevationNico Hartmann0Lena Preuß1Belal A. Mohamed2Moritz Schnelle3Andre Renner4Gerd Hasenfuß5Karl Toischer6Department of Cardiology and Pneumology University Medical Center Göttingen Robert‐Koch‐Str. 40 Göttingen 37075 GermanyDepartment of Cardiology and Pneumology University Medical Center Göttingen Robert‐Koch‐Str. 40 Göttingen 37075 GermanyDepartment of Cardiology and Pneumology University Medical Center Göttingen Robert‐Koch‐Str. 40 Göttingen 37075 GermanyInstitute for Clinical Chemistry University Medical Center Göttingen Göttingen GermanyDepartment of Thoracic, Cardiac and Vascular Surgery (Heart and Diabetes Center) North Rhine Westphalia Bad Oeynhausen GermanyDepartment of Cardiology and Pneumology University Medical Center Göttingen Robert‐Koch‐Str. 40 Göttingen 37075 GermanyDepartment of Cardiology and Pneumology University Medical Center Göttingen Robert‐Koch‐Str. 40 Göttingen 37075 GermanyAbstract Aims Pressure overload (PO) and volume overload (VO) lead to concentric or eccentric hypertrophy. Previously, we could show that activation of signalling cascades differ in in vivo mouse models. Activation of these signal cascades could either be induced by intrinsic load sensing or neuro‐endocrine substances like catecholamines or the renin‐angiotensin‐aldosterone system. Methods and results We therefore analysed the activation of classical cardiac signal pathways [mitogen‐activated protein kinases (MAPKs) (ERK, p38, and JNK) and Akt‐GSK3β] in in vitro of mechanical overload (ejecting heart model, rabbit and human isolated muscle strips). Selective elevation of preload in vitro increased AKT and GSK3β phosphorylation after 15 min in isolated rabbit muscles strips (AKT 49%, GSK3β 26%, P < 0.05) and in mouse ejecting hearts (AKT 51%, GSK49%, P < 0.05), whereas phosphorylation of MAPKs was not influenced by increased preload. Selective elevation of afterload revealed an increase in ERK phosphorylation in the ejecting heart (43%, P < 0.05), but not in AKT, GSK3β, and the other MAPKs. Elevation of preload and afterload in the ejecting heart induced a significant phosphorylation of ERK (95%, P < 0.001) and showed a moderate increased AKT (P = 0.14) and GSK3β (P = 0.21) phosphorylation, which did not reach significance. Preload and afterload elevation in muscles strips from human failing hearts showed neither AKT nor ERK phosphorylation changes. Conclusions Our data show that preload activates the AKT–GSK3β and afterload the ERK pathway in vitro, indicating an intrinsic mechanism independent of endocrine signalling.https://doi.org/10.1002/ehf2.13877HypertrophyPreloadAfterloadAKT‐GSK3βMAPKs |
| spellingShingle | Nico Hartmann Lena Preuß Belal A. Mohamed Moritz Schnelle Andre Renner Gerd Hasenfuß Karl Toischer Different activation of MAPKs and Akt/GSK3β after preload vs. afterload elevation ESC Heart Failure Hypertrophy Preload Afterload AKT‐GSK3β MAPKs |
| title | Different activation of MAPKs and Akt/GSK3β after preload vs. afterload elevation |
| title_full | Different activation of MAPKs and Akt/GSK3β after preload vs. afterload elevation |
| title_fullStr | Different activation of MAPKs and Akt/GSK3β after preload vs. afterload elevation |
| title_full_unstemmed | Different activation of MAPKs and Akt/GSK3β after preload vs. afterload elevation |
| title_short | Different activation of MAPKs and Akt/GSK3β after preload vs. afterload elevation |
| title_sort | different activation of mapks and akt gsk3β after preload vs afterload elevation |
| topic | Hypertrophy Preload Afterload AKT‐GSK3β MAPKs |
| url | https://doi.org/10.1002/ehf2.13877 |
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