In addition to physically occluding the vessel lumen, thrombi act as a physical trap for circulating mitogenic, inflammatory, and vasoreactive factors, many of which can interfere with or alter the function of the adjacent endothelium. Endothelial barrier dysfunction, leading to increased endothelial permeability, is evident in response to barotrauma, inflammation, acute lung injury, and clot retention (33). Changes in shear stress due to vascular occlusion may also influence endothelial cell function and production of vasoreactive and mitogenic factors. Because platelets are a source of numerous inflammatory, vasoactive, mitogenic, and chemotactic factors (e.g., thromboxane A2, serotonin, platelet-activating factor, angiopoietin-1), their aggregation in the thrombus should influence endothelial function. In summary, a retained clot in the pulmonary vascular tree is thought to be an instigator of endothelial permeability, resulting in access of growth factors, cytokines, mitogens, and vasoreactive factors to both pulmonary artery endothelial cells and pulmonary artery smooth muscle cells. There is also preliminary evidence that thromboemboli in the proximal pulmonary arterial tree contains EPCs that migrate into the vessel wall and contribute to the remodeling process (34).