Apolipoprotein B (ApoB) is the primary structural protein in low-density and very low-density lipoproteins, and in chylomicrons. In addition to its established role in lipid metabolism, we have suggested in the past that ApoB negatively regulates angiogenesis during embryonic development. In this work we have used Talen and crispr technologies to generate zebrafish carrying mutations in two ApoB genes- apoBa and apoBb.1. In addition to complete depletion of lipoprotein production and secretion, the double mutant embryos were characterized by excessive angiogenesis. In contrast, a complementary model of hyperlipidemia and increased ApoB secretion, generated through overexpression of microsomal triglyceride transfer protein (mtp), resulted in inhibition of intersegmental vessel formation. Surprisingly, we have been able to detect the presence of ApoB inside the nucleus of endothelial cells both in cultured HUVECs and in FACS sorted zebrafish endothelial cells. These findings suggest that in addition to its well-established role in cholesterol transport, ApoB may act as a regulator of gene expression, functioning according to the metabolic state of tissues.