Research

Role of pericytes in PAH

Pulmonary arterial hypertension (PAH) is a life-threatening disorder that is associated with abnormal increase in pulmonary pressures resulting from progressive loss and impaired regeneration of pulmonary microvessels. A key event in the formation of functional vascular networks is coating of vascular tubes with pericytes, highly specialized vascular cells that directly interact with endothelial cells to provide support and protection to the endothelium. I found PAH pericytes fail to associate with healthy pulmonary endothelial cells during vascular network formation and exhibit abnormal expression of genes involved in the Wnt/Planar cell polarity (PCP), a pathway involved in orchestrating cell motility and alignment during tissue formation.   I propose that (1) activation of Wnt/PCP is necessary for PAEC and pericyte organization into functional pulmonary arteries and (2) that mutations that reduce Wnt/PCP activity impair pulmonary vascular regeneration after injury.  Thus, Wnt/PCP activation caused by Wnt5a-ROR2 signaling may be a therapeutic target for the treatment of impaired pericyte-edothelial cells interactions in PAH.