Altered mechanical state in the embryonic heart re

Authors: Brennan Johnson David Bark Ilse Van Herck Deborah Garrity Lakshmi Prasad Dasi

Publish Date: 2015/05/15

Volume: 14, Issue: 6, Pages: 1379-1389

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Abstract

Proper blood flow patterns are critical for normal cardiac morphogenesis a process that occurs rapidly in order to support further development of all tissue and organs Previously intracardiac fluid forces have been shown to play a critical role in cardiac morphogenesis Altered blood flow in early development can result in an array of cardiac defects including ventricular septal defects valve malformations and impaired cardiac looping However given the dynamic and highly transient nature of cardiac morphogenesis time dependency of the mechanical environment as an epigenetic factor in relation to intracardiac forces must be significant Here we show that abnormal cardiac loading adversely influences cardiac morphology only during certain time windows thus confirming that mechanical factors are a timedependent epigenetic factor To illustrate this groups of zebrafish embryos were spaced at 6h increments from 24 to 48 h postfertilization hpf in which embryos were centrifuged to generate a noninvasive alteration of cardiac preload in addition to an overall hypergravity environment We found that earlier and later treatment groups responded with altered morphology and function while the group with altered preload from 30 to 36 hpf had no effect These results demonstrate the inherently timedependent nature of epigenetic factors as pertaining to intracardiac forces and external mechanical factors Further it underscores the highly coupled nature of programmed biology and mechanical forces during cardiac morphogenesis Future studies with respect to surgical correction during cardiac morphogenesis must consider timing to optimize therapeutic impact

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