Endothelial dysfunction in pulmonary arterial hypertension: an evolving landscape (2017 Grover Conference Series):
Benoît Ranchoux,Lloyd D. Harvey,Ramon J. Ayon,Aleksandra Babicheva,Sébastien Bonnet,Stephen Y. Chan,Jason X.-J. Yuan,Vinicio A. de Jesus Perez +7 more
TLDR
The present review will provide a perspective on the most promising aspects of endothelial dysfunction that may be amenable for therapeutic development as one of the major topics included in the 2017 Grover Conference Series.Abstract:
Endothelial dysfunction is a major player in the development and progression of vascular pathology in pulmonary arterial hypertension (PAH), a disease associated with small vessel loss and obstructive vasculopathy that leads to increased pulmonary vascular resistance, subsequent right heart failure, and premature death. Over the past ten years, there has been tremendous progress in our understanding of pulmonary endothelial biology as it pertains to the genetic and molecular mechanisms that orchestrate the endothelial response to direct or indirect injury, and how their dysregulation can contribute to the pathogenesis of PAH. As one of the major topics included in the 2017 Grover Conference Series, discussion centered on recent developments in four areas of pulmonary endothelial biology: (1) angiogenesis; (2) endothelial-mesenchymal transition (EndMT); (3) epigenetics; and (4) biology of voltage-gated ion channels. The present review will summarize the content of these discussions and provide a perspective on the most promising aspects of endothelial dysfunction that may be amenable for therapeutic development.read more
Citations
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Journal ArticleDOI
Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases.
TL;DR: The identification of molecules and regulatory pathways involved in EndMT and the discovery of specific EndMT inhibitors should provide novel therapeutic approaches for various human disorders mediated by EndMT.
Journal ArticleDOI
Endothelial cells in the pathogenesis of pulmonary arterial hypertension.
Colin E. Evans,Colin E. Evans,Nicholas D Cober,Nicholas D Cober,Zhiyu Dai,Zhiyu Dai,Zhiyu Dai,Duncan J. Stewart,Duncan J. Stewart,You Yang Zhao +9 more
TL;DR: In this article, the authors describe how EC dysfunction and cell signalling regulate the pathogenesis of pulmonary arterial hypertension (PAH), and discuss potential molecular signalling pathways in ECs that could be targeted therapeutically in the prevention and treatment of PAH.
Journal ArticleDOI
Loss of Endothelium-Derived Wnt5a Is Associated With Reduced Pericyte Recruitment and Small Vessel Loss in Pulmonary Arterial Hypertension
Ke Yuan,Ke Yuan,Elya A. Shamskhou,Elya A. Shamskhou,Mark Orcholski,Mark Orcholski,Abinaya Nathan,Abinaya Nathan,Sushma Reddy,Sushma Reddy,Hiroaki Honda,Vigneshwaran Mani,Yitian Zeng,Mehmet Ozgun Ozen,Mehmet Ozgun Ozen,Lingli Wang,Lingli Wang,Utkan Demirci,Wen Tian,Wen Tian,Wen Tian,Mark R. Nicolls,Mark R. Nicolls,Mark R. Nicolls,Vinicio A. de Jesus Perez,Vinicio A. de Jesus Perez +25 more
TL;DR: Wnt5a is identified as a key mediator for the establishment of pulmonary endothelium-pericyte interactions, and its loss could contribute to PAH by reducing the viability of newly formed vessels.
Journal ArticleDOI
Therapeutic potential of KLF2-induced exosomal microRNAs in pulmonary hypertension
Hebah A. Sindi,Giusy Russomanno,Sandro Satta,Vahitha B. Abdul-Salam,Kyeong Beom Jo,Basma Qazi-Chaudhry,Alexander J. Ainscough,Robert Szulcek,Harm Jan Bogaard,Claire Morgan,Soni Savai Pullamsetti,Soni Savai Pullamsetti,Mai M. Alzaydi,Mai M. Alzaydi,Christopher J. Rhodes,Roberto Piva,Christina A. Eichstaedt,Ekkehard Grünig,Martin R. Wilkins,Beata Wojciak-Stothard +19 more
TL;DR: It is shown that KLF2-induced exosomal microRNAs, miR-181a-5p andMiR-324- 5p act together to attenuate pulmonary vascular remodelling and that their actions are mediated by Notch4 and ETS1 and other key regulators of vascular homoeostasis.
Journal ArticleDOI
Beyond the Lungs: Systemic Manifestations of Pulmonary Arterial Hypertension
Nils Nickel,Ke Yuan,Peter Dorfmüller,Steeve Provencher,Yen-Chun Lai,Sébastien Bonnet,Eric D. Austin,Carl D. Koch,Alison Morris,Frédéric Perros,David Montani,Roham T. Zamanian,Vinicio A. de Jesus Perez +12 more
TL;DR: A paradigm in which metabolic abnormalities, genetic injury and systemic vascular dysfunction contribute to systemic manifestations in PAH is proposed, which opens exciting research possibilities, but also encourages clinicians to consider extrapulmonary manifestations in their management of PAH patients.
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