High-density lipoproteins reduce endothelial-to-mesenchymal transition

Abstract

Objective - Endothelial-to-mesenchymal transition is an inflammation-induced process by which endothelial cells can transdifferentiate into fibroblasts. Based on the endothelial-protective and antifibrotic effects of high-density lipoproteins (HDL), we aimed to investigate whether HDL can reduce endothelial-to-mesenchymal transition. Approach and Results - Therefore, human aortic endothelial cells were stimulated with the profibrotic factor transforming growth factor (TGF)-β1 in the presence or absence of HDL. Their impact on the transition of endothelial cells to mesenchymal-like cells was analyzed. Phase contrast microscopy demonstrated that HDL abrogated the TGF-β1-induced spindle-shape morphology in human aortic endothelial cells. Furthermore, HDL decreased the TGF-β1-mediated induction of α-smooth muscle actin expression and concomitant loss in endothelial cadherin expression, as shown by immunofluorescence staining and flow cytometry. In addition, HDL decreased the TGF-β1-induced collagen deposition in human aortic endothelial cells involving the scavenger receptor class B, type 1 and downstream phosphatidyl inositol-3-kinase following the findings that the HDL-mediated reduction was abrogated by scavenger receptor class B, type 1 siRNA knockdown and phosphatidyl inositol-3-kinase inhibition, respectively. The HDL-mediated reduction in endothelial-to-mesenchymal transition was associated with an induction of the inhibitory Smad, Smad 7. Conclusions - We provide the first in vitro evidence that the endothelial-protective and antifibrotic effects of HDL include the reduction in endothelial-to-mesenchymal transition.