Endothelial to Mesenchymal Transition Contributes to Endothelial Dysfunction in Pulmonary Artery Hypertension.

Endothelial to Mesenchymal Transition Contributes to Endothelial Dysfunction in Pulmonary Artery Hypertension. Am J Pathol. 2015 May 5; Authors: Good RB, Gilbane AJ, Trinder SL, Denton CP, Coghlan G, Abraham DJ, Holmes AM Abstract Pulmonary arterial hypertension is a progressive disease characterized by lung endothelial cell dysfunction and vascular remodeling. Normally, the endothelium forms an integral cellular barrier to regulate vascular homeostasis. During embryogenesis endothelial cells exhibit substantial plasticity that contribute to cardiac development by undergoing endothelial-to-mesenchymal transition (EndoMT). Here, we determined the presence of EndoMT in the pulmonary vasculature in vivo and the functional effects of pulmonary artery endothelial cells (PAECs) that undergo EndoMT in vitro. Histologic assessment of pulmonary vessels from patients with systemic sclerosis-associated pulmonary arterial hypertension and the hypoxia/SU5416 mouse model identified the presence von Willebrand factor/α-smooth muscle actin-positive endothelial cells in up to 5% of pulmonary vessels. Induced EndoMT in PAECs by inflammatory cytokines IL-1β, tumor necrosis factor α, and transforming growth factor β led to actin cytoskeleton reorganization and the development of a mesenchymal morphology. Induced EndoMT cells exhibited up-regulation of mesenchymal markers, including collagen type I and α-smooth muscle actin, and a reduction in end...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research