The Hypothesis of “Embryonic Recall”: Mechanotransduction as Common Denominator Linking Normal Cardiogenesis to Recovery in Adult Failing Hearts
Cardiac regeneration remains a clinical target regardless of numerous therapeutic concepts. We formulated a hypothesis claiming that periodic coronary venous pressure elevation (PICSO; Pressure controlled Intermittent Coronary Sinus Occlusion) initiates embedded, but dormant developmental processes...
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-04-01
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| Series: | Journal of Cardiovascular Development and Disease |
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| Online Access: | http://www.mdpi.com/2308-3425/1/1/73 |
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| author | Werner Mohl Dejan Milasinovic Thomas Aschacher Alem Jusic Abudunaibi Maimaitiaili Frank Rattay |
| author_facet | Werner Mohl Dejan Milasinovic Thomas Aschacher Alem Jusic Abudunaibi Maimaitiaili Frank Rattay |
| author_sort | Werner Mohl |
| collection | DOAJ |
| description | Cardiac regeneration remains a clinical target regardless of numerous therapeutic concepts. We formulated a hypothesis claiming that periodic coronary venous pressure elevation (PICSO; Pressure controlled Intermittent Coronary Sinus Occlusion) initiates embedded, but dormant developmental processes in adult jeopardized hearts. Hemodynamics in the primitive beating heart tube is sensed transducing “mechanical” epigenetic information during normal cardiac development. In analogy mechanotransduction via shear stress and pulsatile stretch induced by periodic elevation of blood pressure in cardiac veins reconnects this dormant developmental signal, setting regenerative impulses in the adult heart. Significant increase of hemeoxygenase-1 gene expression (p < 0.001) and vascular endothelial growth factor (VEGF) (p < 0.002) as well as production of VEGRF2 in experimental infarction underscores the resurgence of developmental stimuli by PICSO. Molecular findings correspond with risk reduction (p < 0.0001) in patients with acute coronary syndromes as well as observations in heart failure patients showing substantial risk reduction up to 5 years endorsing our hypothesis and preclinical experience that PICSO via hemodynamic power activates regenerative processes also in adult human hearts. These results emphasize that our proposed hypothesis “embryonic recall” claiming revival of an imbedded albeit dormant “epigenetic” process is able not only to sculpture myocardium in the embryo, but also to redesign structure in the adult and failing heart. |
| first_indexed | 2024-12-12T16:25:48Z |
| format | Article |
| id | doaj.art-9d713fbc37b748f4a2b6322126c16c0e |
| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-12-12T16:25:48Z |
| publishDate | 2014-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-9d713fbc37b748f4a2b6322126c16c0e2022-12-22T00:18:53ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252014-04-0111738210.3390/jcdd1010073jcdd1010073The Hypothesis of “Embryonic Recall”: Mechanotransduction as Common Denominator Linking Normal Cardiogenesis to Recovery in Adult Failing HeartsWerner Mohl0Dejan Milasinovic1Thomas Aschacher2Alem Jusic3Abudunaibi Maimaitiaili4Frank Rattay5Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, AustriaInstitute for Analysis and Scientific Computing, Vienna University of Technology, 1040 Vienna, AustriaCardiac regeneration remains a clinical target regardless of numerous therapeutic concepts. We formulated a hypothesis claiming that periodic coronary venous pressure elevation (PICSO; Pressure controlled Intermittent Coronary Sinus Occlusion) initiates embedded, but dormant developmental processes in adult jeopardized hearts. Hemodynamics in the primitive beating heart tube is sensed transducing “mechanical” epigenetic information during normal cardiac development. In analogy mechanotransduction via shear stress and pulsatile stretch induced by periodic elevation of blood pressure in cardiac veins reconnects this dormant developmental signal, setting regenerative impulses in the adult heart. Significant increase of hemeoxygenase-1 gene expression (p < 0.001) and vascular endothelial growth factor (VEGF) (p < 0.002) as well as production of VEGRF2 in experimental infarction underscores the resurgence of developmental stimuli by PICSO. Molecular findings correspond with risk reduction (p < 0.0001) in patients with acute coronary syndromes as well as observations in heart failure patients showing substantial risk reduction up to 5 years endorsing our hypothesis and preclinical experience that PICSO via hemodynamic power activates regenerative processes also in adult human hearts. These results emphasize that our proposed hypothesis “embryonic recall” claiming revival of an imbedded albeit dormant “epigenetic” process is able not only to sculpture myocardium in the embryo, but also to redesign structure in the adult and failing heart.http://www.mdpi.com/2308-3425/1/1/73cardiac regenerationsystems biologycardiac veinscardiac developmentPICSO |
| spellingShingle | Werner Mohl Dejan Milasinovic Thomas Aschacher Alem Jusic Abudunaibi Maimaitiaili Frank Rattay The Hypothesis of “Embryonic Recall”: Mechanotransduction as Common Denominator Linking Normal Cardiogenesis to Recovery in Adult Failing Hearts Journal of Cardiovascular Development and Disease cardiac regeneration systems biology cardiac veins cardiac development PICSO |
| title | The Hypothesis of “Embryonic Recall”: Mechanotransduction as Common Denominator Linking Normal Cardiogenesis to Recovery in Adult Failing Hearts |
| title_full | The Hypothesis of “Embryonic Recall”: Mechanotransduction as Common Denominator Linking Normal Cardiogenesis to Recovery in Adult Failing Hearts |
| title_fullStr | The Hypothesis of “Embryonic Recall”: Mechanotransduction as Common Denominator Linking Normal Cardiogenesis to Recovery in Adult Failing Hearts |
| title_full_unstemmed | The Hypothesis of “Embryonic Recall”: Mechanotransduction as Common Denominator Linking Normal Cardiogenesis to Recovery in Adult Failing Hearts |
| title_short | The Hypothesis of “Embryonic Recall”: Mechanotransduction as Common Denominator Linking Normal Cardiogenesis to Recovery in Adult Failing Hearts |
| title_sort | hypothesis of embryonic recall mechanotransduction as common denominator linking normal cardiogenesis to recovery in adult failing hearts |
| topic | cardiac regeneration systems biology cardiac veins cardiac development PICSO |
| url | http://www.mdpi.com/2308-3425/1/1/73 |
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