Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension

E Arciniegas, MG Frid, IS Douglas… - American Journal of …, 2007 - journals.physiology.org
E Arciniegas, MG Frid, IS Douglas, KR Stenmark
American Journal of Physiology-Lung Cellular and Molecular …, 2007journals.physiology.org
All forms of pulmonary hypertension are characterized by structural changes in pulmonary
arteries. Increased numbers of cells expressing α-smooth muscle (α-SM) actin is a nearly
universal finding in the remodeled artery. Traditionally, it was assumed that resident smooth
muscle cells were the exclusive source of these newly appearing α-SM actin-expressing
cells. However, rapidly emerging experimental evidence suggests other, alternative cellular
sources of these cells. One possibility is that endothelial cells can transition into …
All forms of pulmonary hypertension are characterized by structural changes in pulmonary arteries. Increased numbers of cells expressing α-smooth muscle (α-SM) actin is a nearly universal finding in the remodeled artery. Traditionally, it was assumed that resident smooth muscle cells were the exclusive source of these newly appearing α-SM actin-expressing cells. However, rapidly emerging experimental evidence suggests other, alternative cellular sources of these cells. One possibility is that endothelial cells can transition into mesenchymal cells expressing α-SM actin and that this process contributes to the accumulation of SM-like cells in vascular pathologies. We review the evidence that endothelial-mesenchymal transition is an important contributor to cardiac and vascular development as well as to pathophysiological vascular remodeling. Recent work has provided evidence for the role of transforming growth factor-β, Wnt, and Notch signaling in this process. The potential roles of matrix metalloproteinases and serine proteases are also discussed. Importantly, endothelial-mesenchymal transition may be reversible. Thus insights into the mechanisms controlling endothelial-mesenchymal transition are relevant to vascular remodeling and are important as we consider new therapies aimed at reversing pulmonary vascular remodeling.
American Physiological Society