Altered pericyte function with metabolic comorbidities and the effects on cognitive function

OVERALL AIM： To show that Pitx2 downregulation initiates the process of vessel regression and to understand whether preventing Pitx2 downregulation would prevent vascular rarefaction in the brain. Research Methodology：1.Analysis of vascular density and cognitive function in mice in which Pitx2 is ablated. 2. Analysis of vascular density/microvascular function and cognitive function in mice exposed to metabolic comorbidities. 3. Analysis of main shear-activated signaling pathways, and effect on Pitx2 activation by low shear stress. 4. RNA-Seq of endothelial cells with and without constitutively expressed Pitx2. 5. Analysis of endothelial cell response to low shear stress with constitutively expressed Pitx2. 6. Analysis of Pitx2 expression and vascular rarefaction in mice with hypoperfusion secondary to pericyte loss (PDGFBret/ret).