Abstract
The pathogenetic role of angiogenesis in interstitial lung diseases (ILD) is controversial. This study represents the first investigation of the spatial complexity and molecular motifs of microvascular architecture in important subsets of human ILD.
The aim of our study was to identify specific variants of neoangiogenesis in three common pulmonary injury patterns in human ILD.
We performed comprehensive and compartment-specific analysis of a total of 24 human lung explants with UIP, NSIP and AFE using histopathology, microvascular corrosion casting, µCT-based volumetry, and gene expression analysis using Nanostring as well as immunohistochemistry to assess remodeling-associated angiogenesis.
Morphometrical assessment of vessel diameters and intervascular distances showed significant differences in neoangiogenesis in characteristically remodeled areas of UIP, NSIP, and AFE lungs. Likewise, gene expression analysis revealed distinct and specific angiogenic profiles in UIP, NSIP and AFE lungs.
Whereas UIP lungs showed a higher density of upstream vascularity and lower density in perifocal blood vessels, NSIP and AFE lungs revealed densely packed alveolar septal blood vessels. Vascular remodeling in NSIP and AFE is characterised by a prominent intussusceptive neoangiogenesis, in contrast to UIP, in which sprouting of new vessels into the fibrotic areas is characteristic. The molecular analyses of the gene expression provide a foundation for understanding these fundamental differences between AFE and UIP and give insight into the involved cellular functions.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Ackermann has no conflict/no disclosures.
Conflict of interest: Dr. Stark has nothing to disclose.
Conflict of interest: Dr. Neubert has nothing to disclose.
Conflict of interest: Dr. Schubert has nothing to disclose.
Conflict of interest: Dr. Borchert has nothing to disclose.
Conflict of interest: Dr Linz has no conflict/no disclosures
Conflict of interest: Dr. Wagner has nothing to disclose.
Conflict of interest: Dr. Wielpütz reports grants from Boehringer Ingelheim, grants from Vertex Pharma, outside the submitted work.
Conflict of interest: Anne Höfer has nothing to disclose.
Conflict of interest: Dr. Haverich has nothing to disclose.
Conflict of interest: Dr. Mentzer has nothing to disclose.
Conflict of interest: Dr. Shah has nothing to disclose.
Conflict of interest: Dr. Welte reports grants from German Ministry of Research and Education, during the conduct of the study; personal fees from Boehringer Ingelheim, personal fees from Roche, outside the submitted work.
Conflict of interest: Dr. Jonigk has nothing to disclose.
Conflict of interest: Dr. Stiller reports grants from German Federal Ministry of Education and Research (BMBF), during the conduct of the study.
Conflict of interest: Dr. Kühnel has nothing to disclose.
- Received May 9, 2019.
- Accepted November 25, 2019.
- Copyright ©ERS 2019
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