Transciptional effects of coronary vessel loss on epicaridal cells in juvenile zebrafish

We further demonstrate that epicardial subpopulations are required for both coronary development and myocardial expansion. Using cxcr4aum20 mutants lacking functional coronary vessels, we show that coronary vessels function as a negative feedback mechanism to epicardial hypoxia, while positively responding to the same hypoxic cues that drive myocardial expansion. Importantly, disruption of this negative feedback on epicardial hypoxia also leads to increased myocardial stiffness through dysregulated extracellular matrix crosslinking.

Thus, we provide mechanistic insights into pathological conditions characterized by myocardial stiffness such as cardiomyopathies. These findings establish the role of regional epicardial hypoxia within a fundamental regulatory network that drives appropriate regional tissue growth with integrated vascular supply during cardiac morphogenesis.