Pulmonary Artery Endothelial Cell Barrier Function
Among the most difficult clinical issues to manage is acute respiratory distress syndrome (ARDS). Mortality rates are high as well as considerable morbidity. For reasons that remain incompletely understood, children with ARDS are more likely to survive than adults with similar severity of illness. Our laboratory has been interested in the reasons that underlie the seemingly more well-preserved barrier function in children compared to adults. Using cell lines and a murine model of lung injury, we have identified that the expression of focal adhesion kinase, a molecule responsible for maintaining barrier function increases in expression increases more rapidly in response to either an inflammatory stimulus or hypoxia.
Projects
Cellular Stress Induces Pulmonary Artery Endothelial Cell Differentiation
Researchers: Elizabeth A. Barnes, David N. Cornfield
PH EC are easily affected by cellular stress. They produce more VWF due to EC injury. Herein, we show that stress triggers EC differentiation in PAEC from PH patients.
Control PAEC exposed to starvation media do not change (panel B); in contrast, PH PAEC exposed to starvation media change their phenotype (panel D). Magnification 200x, calibration bar 100mm. Expression of VE-cadherin (red), F-actin (green), and nuclei (blue) are pictured.
Endothelial Cells from Pulmonary Hypertensive Patients Secrete VWF to Alter PH SMC Gene Expression
Researchers: Elizabeth A. Barnes, David N. Cornfield
It has been demonstrated that PAEC from PH patients secrete significant amounts of VWF, a protein involved in PAEC repair. And it has also been demonstrated that SMC exposed to VWF change their transcriptional profile, suggesting that PASMC from PH patients have changed and do not behave like normal PASMC. This event may play a role in the pathogenesis of PH.
Smooth Muscle Cells from Pulmonary Hypertensive Patients Secrete BMP2 to Induce Endothelial Cell Aberrant Angiogenesis
Researchers: Elizabeth A. Barnes, David N. Cornfield
It has been demonstrated that pulmonary artery endothelial cells (PAEC) that are devoid of functional BMPR2 become migratory when stimulated with BMP2, the ligand for BMPR2. We have found that SMC from patients with PH secrete BMP2 and promote PAEC dysfunctional migration. This event plays a key role in the pathogenesis of PH.
BMP2-induced angiogenesis. PAEC and PASMC from PH patients display dysfunctional angiogenesis in the presence of BMP2 (lower middle panel). Arrows represent small disorganized vascular masses. With the addition of exogenous BMP2, PAEC and PASMC from PH patients display further dysfunctional angiogenesis (lower right panel). Magnification 200x.
People
Elizabeth A. Barnes, Ph.D.
