Role Of Microtubule Cytoskeleton As A New Target For Pulmonary Hypertension Management

Hypoxia is one of the most powerful triggers for neonatal Pulmonary Hypertension (PH) acting directly on endothelial cells (ECs). Translocation of hypoxia inducible factors (HIFs) into nucleus plays a critical role in the pathogenesis of PH by inducing transcription of genes containing hypoxia response elements (HRE) like endothelin1 (ET1). The microtubule (MT) cytoskeleton provides the scaffold for movement of different cell elements. MT-associated End Binding protein (EB3) is core element of dynamic network at the growing MT tips that promotes MT growth and establishes the interactions with intracellular structures. The objective of these studies is to test the role of EB3 in facilitating the adaptation of endothelial cells to hypoxic stress through stabilization and/or nuclear translocation of HIFs and induction of ET-1(Fig.1). To compare the role of EB3 in ECs and Smooth Muscle Cells (SMCs) in PH, we developed inducible cell type specific Knock Out (KO) mouse …