Lineage Analysis in Pulmonary Arterial Hypertension
Annual rept. 15 May 2010 - 14 May 2011
LELAND STANFORD JUNIOR UNIV CA
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Pulmonary arterial hypertension is characterized by inappropriate proliferation of neointimal cells that occlude the lumen of the microcirculation leading to right ventricular congestive failure and death. The neointimal cells express disorganized fibrils of smooth muscle actin. The origin of the neointimal cells remains unresolved the neointima may arise from de-differentiation of vascular smooth muscle cells or from microvascular endothelial progenitor cells undergoing endothelial-to-mesenchymal transition. Aim 1 is to determine how endothelial to mesenchymal transition may contribute to neointimal vascular occlusion in pulmonary hypertension using genetic lineage marking in mice. Aim 2 is to characterize how Notch signaling regulates endothelial to mesenchymal transition. During the current funding period, successful Cre-lox genetic labeling of the endothelial lineage was achieved, and specificity of endothelial genetic lineage marking was confirmed by co-immunostaining of endothelial antigens, CD31 and VE-Cadherin. Successful induction of experimental pulmonary hypertension was achieved and demonstrated extensive contribution of endothelial genetic lineage-marked cells to neointimal vascular occlusion.
- Anatomy and Physiology
- Medicine and Medical Research