The Cardiovascular Triad of Dysfunctional Angiogenesis
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REVIEW
The Cardiovascular Triad of Dysfunctional Angiogenesis Jun Zhang & Chris Carr & Ahmed Badr
Received: 8 September 2010 / Revised: 8 January 2011 / Accepted: 11 January 2011 / Published online: 29 January 2011 # Springer Science+Business Media, LLC 2011
Abstract 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. Keywords Cerebral cavernous malformation . Stroke . Microvascular malformation . Cardiovascular triad . Angiogenesis . Cardiovascular defects . Animal models . Zebrafish J. Zhang (*) : A. Badr COE for Neurosciences, Department of Anesthesiology, Texas Tech University Health Science Center, 4800 Alberta Avenue, El Paso, TX 79905, USA e-mail: [email protected] C. Carr Emory University School of Medicine, Atlanta, GA 30322, USA
Introduction With the advent of zebrafish transgenesis and imaging technology, any single vascular endotholial cell along the vasculature can be analyzed in the zebrafish. Endotheliumspecific GFP-labeled zebrafish lines provide a powerful tool to dissect angiogenic events during embryonic development. Therefore, these transgenic zebrafish lines have been considered as the potential model to study human strokes. However, on the mutant zebrafish model of cerebral cavernous malformation, one clinical type of the human stroke, there is obvious phenotypic discrepancy between humans and animal models. Although the zebrafish models still provide great details in studying angiogenesis, understanding the etiology of the phenotypic discrepancy between humans and zebrafish models would greatly enhance our future translational research on human stroke. Cerebral cavernous malformations (CCMs), also known as cavernous angiomas or cavernomas, are vascular malformations in the brain with a characteristic MRI appearance. CCMs account for 10–15% of a
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