Journal Article Epublish
PubMed: 40463493 DOI: 10.1002/pul2.70102
Ectopic Expansion of Pulmonary Vasculature in Fibrotic Lung Disease and Lung Adenocarcinoma Marked by Proangiogenic COL15A1+ Endothelial Cells.
Pulm Circ 15(2):e70102
Authors: Eric Engelbrecht, Tristan Kooistra, Nathalie Burg, Lida Hariri, Trong Nguyen, Patricia Brazee, Timothy Hla, Bernadette R Gochuico, Rachel S Knipe
Affiliations
- University of Louisville School of Medicine Louisville Kentucky USA.
- Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital Harvard Medical School Boston Massachusetts USA.
- Department of Rheumatology, Hospital for Special Surgery Cornell University NY New York USA.
- Department of Pathology, Massachusetts General Hospital Harvard Medical School Boston Massachusetts USA.
- Children's Hospital, and Department of Surgery, Vascular Biology Program Harvard Medical School Boston USA.
- Medical Genetics Branch, National Human Genome Research Institute National Institutes of Health Bethesda Maryland USA.
Abstract
Lung vasculature arises from both pulmonary and systemic (bronchial) circulations. Remodeling and structural changes in lung vasculature have been recognized in end-stage fibrotic lung diseases such as idiopathic pulmonary fibrosis (IPF) but have not been well characterized. The vasculature that expands and supplies lung cancers is better described, with the recent recognition that systemic bronchial circulation expands to be the main blood supply to primary lung tumors. Here, we use publicly available single-cell RNA-sequencing (scRNA-seq) data to compare vascular endothelial cell (EC) populations in multiple progressive interstitial lung diseases (ILD) and non-small cell lung cancer (NSCLC) to identify common and distinct features. Lung tissue specimens were collected from healthy lung tissue (n = 59), ILD (n = 97), chronic obstructive pulmonary disease (n = 22), and NSCLC (n = 8). We identify two subtypes of expanded EC populations in both ILD and NSCLC, "Bronch-1" and "Bronch-2", expressing transcripts associated with venules and angiogenic tip/stalk cells, respectively. Relative to pulmonary capillary and arterial ECs, bronchial ECs show low expression of transcripts associated with vascular barrier integrity. The pan-bronchial EC marker COL15A1 showed positive staining in lung parenchyma from patients with IPF, SSc-ILD, and NSCLC, whereas positive staining was limited to subpleural and peri-bronchial regions in non-fibrotic controls. In conclusion, expansion of a subset of ECs expressing markers of the bronchial circulation is one of the most pronounced changes in vascular cell composition across multiple ILDs and NSCLC. These data support additional studies to determine the role of the bronchial vasculature in ILD progression.
MeSH
Cells, Lung, Neoplasms, Adenocarcinoma, Carcinoma, Non-Small-Cell Lung, Adenocarcinoma Of Lung, Lung Neoplasms, Pulmonary Fibrosis, Endothelial Cells, Lung Diseases, Tissues, Endothelium