Reversal of Emphysema by Restoration of Pulmonary Endothelial Cells

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2021 Jul 21

PMID 34287647

Citations 33

Authors

Shu Hisata

Alexandra C Racanelli

Pouneh Kermani

Ryan Schreiner

Sean Houghton

Brisa Palikuqi

Balvir Kunar

Aiyuan Zhou

Keith McConn

Allyson Capili

David Redmond

Daniel J Nolan

Michael Ginsberg

Bi-Sen Ding

Fernando J Martinez

Joseph M Scandura

Suzanne M Cloonan

Shahin Rafii

Augustine M K Choi

Affiliations

Soon will be listed here.

Abstract

Chronic obstructive pulmonary disease (COPD) is marked by airway inflammation and airspace enlargement (emphysema) leading to airflow obstruction and eventual respiratory failure. Microvasculature dysfunction is associated with COPD/emphysema. However, it is not known if abnormal endothelium drives COPD/emphysema pathology and/or if correcting endothelial dysfunction has therapeutic potential. Here, we show the centrality of endothelial cells to the pathogenesis of COPD/emphysema in human tissue and using an elastase-induced murine model of emphysema. Airspace disease showed significant endothelial cell loss, and transcriptional profiling suggested an apoptotic, angiogenic, and inflammatory state. This alveolar destruction was rescued by intravenous delivery of healthy lung endothelial cells. Leucine-rich α-2-glycoprotein-1 (LRG1) was a driver of emphysema, and deletion of Lrg1 from endothelial cells rescued vascular rarefaction and alveolar regression. Hence, targeting endothelial cell biology through regenerative methods and/or inhibition of the LRG1 pathway may represent strategies of immense potential for the treatment of COPD/emphysema.

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