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Open AccessJournal ArticleDOI

Endothelial dysfunction in pulmonary arterial hypertension: an evolving landscape (2017 Grover Conference Series):

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.

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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.

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

Beyond the Lungs: Systemic Manifestations of Pulmonary Arterial Hypertension

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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TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
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TL;DR: Understanding of the molecular basis underlying angiogenesis, particularly from the study of mice lacking some of the signalling systems involved, has greatly improved, and may suggest new approaches for treating conditions such as cancer that depend onAngiogenesis.
Journal ArticleDOI

Molecular mechanisms and clinical applications of angiogenesis

TL;DR: Preclinical and clinical studies have shown new molecular targets and principles, which may provide avenues for improving the therapeutic benefit from anti-angiogenic strategies.
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