VEGF and its receptors expression in relation to reduced vasculature phenotype in heme oxygenase 1 knockout mouse embryos.

Vascular development is a pivotal aspect of embryogenesis, and its disruption can lead to developmental abnormalities or lethality. Although numerous studies have demonstrated a significant association between heme oxygenase 1 (Hmox1) and vascular biology, this link has not been reported so far during mouse embryonic development. Hmox1 is the rate-limiting enzyme that catalyzes the breakdown of heme to equimolar amounts of biliverdin, carbon monoxide, and ferrous iron. Here, we report that embryos lacking Hmox1 exhibit significant reductions in superficial blood vessel formation during mid-gestation, accompanied by organ-specific disruptions in vascular patterning. A comparative analysis of VEGF, VEGFR2, and CD31 revealed tissue-specific disruptions in angiogenic signaling and endothelial integrity in the brain, heart, and lungs of Hmox1-deficient embryos. The localization and abundance of these molecules were altered in affected organs, with isoform- and receptor subtype-specific expression changes raising the possibility of an impact on the structural integrity of developing vascular networks. These findings suggest that the absence of Hmox1 disrupts essential regulatory mechanisms required for angiogenesis, potentially contributing to the partial prenatal lethality observed in knockout embryos. Our results point to a previously unrecognized role for Hmox1 in regulating organ-specific vascular development during late gestation, with its deficiency leading to tissue-specific disruptions in angiogenesis and impaired blood vessel formation.