Lineage Analysis in Pulmonary Arterial Hypertension
Annual rept. 15 May 2011-14 May 2012
STANFORD UNIV CA
Pagination or Media Count:
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, a subset of pulmonary arterial vascular lining cells was discovered with endothelial genetic lineage and coexpression of smooth muscle antigens, SMA, SM-MHC, and SM22. Induction of experimental pulmonary hypertension with neointima vascular occlusion is associated with augmented expression of smooth muscle antigens in cells of endothelial genetic lineage. Conditional endothelial and smooth muscle lineage marking will be used to determine the principal lineage contributing to the pathologic neointima and suggest novel therapies.
- Anatomy and Physiology
- Medicine and Medical Research