The Hypothesis of “Embryonic Recall”: Mechanotransduction as Common Denominator Linking Normal Cardiogenesis to Recovery in Adult Failing Hearts

Journal of Cardiovascular Development and Disease

Werner Mohl¹  Dejan Milasinovic¹  Thomas Aschacher¹  Alem Jusic¹  Abudunaibi Maimaitiaili¹ 

[1] Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria; E-Mails:

关键词: cardiac regeneration;    systems biology;    cardiac veins;    cardiac development;    PICSO;   

DOI  :  10.3390/jcdd1010073

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.