A, Transgenic fli1:EGFP zebrafish sport green vasculature, mpeg1:EGFP and lyz:DsRed2 have green macrophages or red myeloid cells (brightest red fluorescence in neutrophils and weaker in monocytes and macrophages), and hsp70:IK17-EGFP express the EGFP-tagged anti-malondialdehyde (MDA)-LDL antibody IK17, but only after heat shock (1 hour at 37°C). Feeding either of these transgenic zebrafish a high cholesterol diet initiates vascular processes resembling those that take place during early human atherogenesis. Top image shows a 3D rendering of a blood vessel (green) with lipid-loaded vascular myeloid cells (orange), i.e. foam cells (arrow). Bottom image shows that IK17-EGFP (green) binds to MDA epitopes within vascular lipid deposits (red, because of a red lipid tracer added to the zebrafish diet); the resulting colocalization of green and red displays as yellow (arrow) on the image. B, For angiogenesis studies, the genes/proteins that were modified through a mutation, knockdown, overexpression or pharmacologic inhibition, include mtp (assembles VLDL; stl is an mtp loss-of-function mutant), aibp (facilitates cholesterol efflux from endothelial cells), abca1 and abcg1 (cellular transporters that mediate cholesterol efflux), apoB (the LDL protein), apoC2 (activates lipoprotein lipase), and Hmgcr (enzyme of cholesterol and prenol synthesis pathways). Top-left image shows a zebrafish larva with red box depicting the area where fluorescent images were recorded. Bottom-left is an image of normal subintestinal veins (SIV), and bottom-right is an image of excessive sprouting in the SIV region. Arrows show two ectopic SIV sprouts.