PHA Proof of Concept Research Grant Winner 2015

Ke Yuan, PhD

Ke Yuan, PhD

Instructor, Pulmonary Critical Care Medicine
Stanford University
Title: “The role of lung pericytes as a source of occluding pulmonary artery smooth muscle cells in PAH”
Term: December 1, 2015- November 30, 2016

Summary of Research Project:

Pulmonary arterial hypertension (PAH) is a life-threatening disorder associated with an abnormal increase in lung pressures that, if untreated, lead to heart failure and premature death. While the cause of PAH is unknown, progressive small vessel loss and muscularized distal arterioles due to increased proliferation of arterial smooth muscle cells (SMCs) are major pathological features of this disorder. The source of these SMCs remains poorly understood. Pericytes are resided in distal vessels and help to form normal vessels. No study to date has showed whether pericytes give rise to SMCs occurs in the lung circulation or if pericytes contribute to muscularization of distal vessels in PAH. In this proposal, I will study for the first time pericytes give rise to SMCs and how this process is severely disrupted in PAH resulting in occluded distal vessles. The goal of this proposal is to use novel transgenic mouse models to label pericytes in green color and trace their life cycle and behavior in the lung circulation under hypoxia, a known trigger for muscularization of vessels. We will pursue more studies aimed at unraveling the signaling pathways that regulate the transition of pericytes to SMCs and candidate genes that may be relevant in this process. Understanding the role of pericytes in PAH will result in innovative insights into lung vascular biology and facilitate the discovery of novel therapeutic approaches capable of favorably rescue vessel normal function, such as turning SMCs back to pericytes, and improve clinical outcome.