These findings suggest that all forms of pulmonary hypertension are linked by defects in the signaling pathway involving angiopoietin-1, TIE2, BMPR1A, and BMPR2 and consequently identify specific molecular targets for therapeutic intervention.
Smooth muscle cell proliferation around small pulmonary vessels is essential to the pathogenesis of pulmonary hypertension. Here we describe a molecular mechanism and animal model for this vascular pathology. Rodents engineered to express angiopoietin 1 (Ang-1) constitutively in the lung develop severe pulmonary hypertension. These animals manifest diffuse medial thickening in small pulmonary vessels, resulting from smooth muscle cell hyperplasia. This pathology is common to all forms of human pulmonary hypertension. We demonstrate that Ang-1 stimulates pulmonary arteriolar endothelial cells through a TIE2 (receptor with tyrosine kinase activity containing IgG-like loops and epidermal growth factor homology domains) pathway to produce and secrete serotonin (5-hydroxytryptamine), a potent smooth muscle mitogen, and find that high levels of serotonin are present both in human and rodent pulmonary hypertensive lung tissue. These results suggest that pulmonary hypertensive vasculopathy occurs through an Ang-1͞ TIE2͞serotonin paracrine pathway and imply that these signaling molecules may be targets for strategies to treat this disease.
Objectives: Thoracic endovascular aneurysm repair (TEVAR) was introduced in 2005 to treat descending thoracic aortic aneurysms. Little is known about TEVAR's nationwide effect on patient outcomes. We evaluated nationwide data regarding the short-term outcomes of TEVAR and open aortic repair (OAR) procedures performed in the United States during a 2-year period.Methods: From the Nationwide Inpatient Sample data, we identified patients who had undergone surgery for an isolated descending thoracic aortic aneurysm from 2006 to 2007. Patients with aneurysm rupture, aortic dissection, vasculitis, connective tissue disorders, or concomitant aneurysms in other aortic segments were excluded. Of the remaining 11,669 patients, 9106 had undergone conventional OAR and 2563 had undergone TEVAR. Hierarchic regression analysis was used to assess the effect of TEVAR versus OAR after adjusting for confounding factors. The primary outcomes were mortality and the hospital length of stay (LOS). The secondary outcomes were the discharge status, morbidity, and hospital charges.
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