Exploring molecular regulation of angiogenesis and vascular homeostasis
What We Do
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Here we studied the molecular mechanisms of endothelial cell regeneration in adult vessels. Using a model of aortic injury, we found that regeneration occurs at the edges of the wounded area with equal strength and regardless of flow direction. Through a robust proliferative response, the wound closes by efforts of a rapidly dividing cell population that expresses Atf3.
Here we showed that Notch1 is expressed at high levels in adult large arteries with polarized distribution downstream flow direction. Reversion of flow direction promotes relocation of Notch1 to the other pole of the cells, indicating that Notch is a mechanosensor. Inactivation of Noth1 affects the integrity of endothelial barrier and promotes endothelial proliferation.
A transposon mutagenesis screen revealed that mutations in the hemogenic endothelium can result in hematopoietic pathologies of myeloid and lymphoid nature. The approach identified Pi4ka, a lipid kinase that in this context promotes myeloid and erythroid dysfunction and results in pronounced anemia.
The guanosine nucleotide exchange factor Vav3 promotes high-resistance barrier function to microvascular endothelium. Ectopic expression of Vav3 in large artery and brain endothelial cells significantly enhance barrier resistance and cortical rearrangement of actin cytoskeleton, a process that requires interaction with Rap1.