title: Endothelial Plasticity: Shifting Phenotypes through Force Feedback.
abstract: The endothelial lining of the vasculature is exposed to a large variety of biochemical and hemodynamic stimuli with different gradients throughout the vascular network. Adequate adaptation requires endothelial cells to be highly plastic, which is reflected by the remarkable heterogeneity of endothelial cells in tissues and organs. Hemodynamic forces such as fluid shear stress and cyclic strain are strong modulators of the endothelial phenotype and function. Although endothelial plasticity is essential during development and adult physiology, proatherogenic stimuli can induce adverse plasticity which contributes to disease. Endothelial-to-mesenchymal transition (EndMT), the hallmark of endothelial plasticity, was long thought to be restricted to embryonic development but has emerged as a pathologic process in a plethora of diseases. In this perspective we argue how shear stress and cyclic strain can modulate EndMT and discuss how this is reflected in atherosclerosis and pulmonary arterial hypertension.
authors.affiliation: Cardiovascular Regenerative Medicine Research Group (Cavarem), Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713GZ Groningen, Netherlands.
authors.forename: Guido
authors.initials: G
authors.lastname: Krenning
authors.affiliation: Laboratory of Genetics and Molecular Cardiology (LIM13), Heart Institute (InCor), University of São Paulo, Avenida Dr. Eneas C. Aguiar 44, 05403-000 São Paulo, SP, Brazil; Department of Physiological Sciences, Federal University of Espírito Santo (UFES), Avenida Marechal Campos 1468-Maruípe, 29043-900 Vitoria, ES, Brazil.
authors.forename: Valerio G
authors.initials: VG
authors.lastname: Barauna
authors.affiliation: Laboratory of Genetics and Molecular Cardiology (LIM13), Heart Institute (InCor), University of São Paulo, Avenida Dr. Eneas C. Aguiar 44, 05403-000 São Paulo, SP, Brazil.
authors.forename: José E
authors.initials: JE
authors.lastname: Krieger
authors.affiliation: Cardiovascular Regenerative Medicine Research Group (Cavarem), Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713GZ Groningen, Netherlands.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Harmsen
authors.affiliation: Cardiovascular Regenerative Medicine Research Group (Cavarem), Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713GZ Groningen, Netherlands; Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (CA40), 9713GZ Groningen, Netherlands.
authors.forename: Jan-Renier A J
authors.initials: JR
authors.lastname: Moonen