Cerebral cavernous malformation is a clinically well-defined microvascular disorder predisposing to stroke; however, the major phenotype observed in zebrafish is the cardiac defect, specifically an enlarged heart. Less effort has been made to explore this phenotypic discrepancy between human and zebrafish. Given the fact that the gene products from Ccm1/Ccm2 are nearly identical between the two species, the common sense has dictated that the zebrafish animal model would provide a great opportunity to dissect the detailed molecular function of Ccm1/Ccm2 during angiogenesis. We recently reported on the cellular role of the Ccm1 gene in biochemical processes that permit proper angiogenic microvascular development in the zebrafish model. In the course of this experimentation, we encountered a vast amount of recent research on the relationship between dysfunctional angiogenesis and cardiovascular defects in zebrafish. Here we compile the findings of our research with the most recent contributions in this field and glean conclusions about the effect of defective angiogenesis on the developing cardiovascular system. Our conclusion also serves as a bridge for the phenotypic discrepancy between humans and animal models, which might provide some insights into future translational research on human stroke.