Embryonic recall is a hypothesis claiming that reactivation of developmental processes via gene expression in adult organisms is comparable to gene expression patterns in early embryonic growth stages.
Concept
The hypothesis of embryonic recall defines a regenerative process in the adult failing heart as analogy to the canonical pathway of the developing heart and was proposed in 2007 by Werner Mohl. It claims that periodic coronary venous pressure elevation (PICSO) initiates embedded, but dormant developmental processes in adults during myocardial jeopardy, i.e. after myocardial infarction or heart failure. Hemodynamics in the primitive beating heart tube is sensed transducing “mechanical” epigenetic information during normal heart development into molecular signals. As known from earlier observations, Hemodynamics provides physiological feedback to cardiogenesis.
That cardiogenesis is dependent on the mechanical action of blood flow was found by Miyasaka stating that heartbeat regulates cardiogenesis. Peter Scambler and Lain Dykes in their discussion of Myiasaka´s paper stated that the mechanical stress resulting from blood circulation can sometimes be a factor in heart development as important as more conventional mechanisms such as signalling pathways.
In analogy to cardiogenesis in the adult failing heart the embryonic recall hypothesis claims that mechanotransduction via shear stress and pulsatile stretch induced by periodic elevation of blood pressure in cardiac veins reopens this dormant developmental signal, setting regenerative impulses in the adult heart. Significant increase of Heme oxygenase 1 gene expression and vascular endothelial growth factor (VEGF) as well as production of VEGRF2 in experimental infarction underscores the resurgence of developmental stimuli by PICSO.
Molecular findings correspond with risk reduction in patients with acute coronary syndromes as well as observations in heart failure patients. PICSO induced substantial risk reduction for re-infarction and Mace (major adverse cardiac events) and by an upregulation of soluble factors released into the coronary circulation also in heart failure patients up to 5 years endorsing the hypothesis “embryonic recall”. This clinical and preclinical experience suggest that PICSO via hemodynamic power activates regenerative processes also in adult human hearts reconnecting to pluripotent canonical pathways during cardiogenesis. The results emphasize that the proposed hypothesis “embryonic recall” claiming revival of an imbedded albeit dormant “epigenetic” process common to sculpture myocardium in the embryo, are able to redesign structure in the adult and failing heart.