Aggrecan accumulates at sites of increased pulmonary arterial pressure in idiopathic pulmonary arterial hypertension
(2023) In Pulmonary Circulation 13(1).- Abstract
Expansion of extracellular matrix occurs in all stages of pulmonary angiopathy associated with pulmonary arterial hypertension (PAH). In systemic arteries, dysregulation and accumulation of the large chondroitin-sulfate proteoglycan aggrecan is associated with swelling and disruption of vessel wall homeostasis. Whether aggrecan is present in pulmonary arteries, and its potential roles in PAH, has not been thoroughly investigated. Here, lung tissue from 11 patients with idiopathic PAH was imaged using synchrotron radiation phase-contrast microcomputed tomography (TOMCAT beamline, Swiss Light Source). Immunohistochemistry for aggrecan core protein in subsequently sectioned lung tissue demonstrated accumulation in PAH compared with failed... (More)
Expansion of extracellular matrix occurs in all stages of pulmonary angiopathy associated with pulmonary arterial hypertension (PAH). In systemic arteries, dysregulation and accumulation of the large chondroitin-sulfate proteoglycan aggrecan is associated with swelling and disruption of vessel wall homeostasis. Whether aggrecan is present in pulmonary arteries, and its potential roles in PAH, has not been thoroughly investigated. Here, lung tissue from 11 patients with idiopathic PAH was imaged using synchrotron radiation phase-contrast microcomputed tomography (TOMCAT beamline, Swiss Light Source). Immunohistochemistry for aggrecan core protein in subsequently sectioned lung tissue demonstrated accumulation in PAH compared with failed donor lung controls. RNAscope in situ hybridization indicated
(Less)
ACAN expression in vascular endothelium and smooth muscle cells. Based on qualitative histological analysis, aggrecan localizes to cellular, rather than fibrotic or collagenous, lesions. Interestingly,
ADAMTS15, a potential aggrecanase, was upregulated in pulmonary arteries in PAH. Aligning traditional histological analysis with three-dimensional renderings of pulmonary arteries from synchrotron imaging identified aggrecan in lumen-reducing lesions containing loose, cell-rich connective tissue, at sites of intrapulmonary bronchopulmonary shunting, and at sites of presumed elevated pulmonary blood pressure. Our findings suggest that
ACAN expression may be an early response to injury in pulmonary angiopathy and supports recent work showing that dysregulation of aggrecan turnover is a hallmark of arterial adaptations to altered hemodynamics. Whether cause or effect, aggrecan and aggrecanase regulation in PAH are potential therapeutic targets.
- author
- organization
-
- Vessel Wall Biology (research group)
- Medical Radiation Physics, Lund
- LTH Profile Area: Engineering Health
- X-ray Phase Contrast (research group)
- Lund OsteoArthritis Division - Molecular marker research group (research group)
- LUCC: Lund University Cancer Centre
- Improved diagnostics and prognostics of lung cancer and metastases to the lungs (research group)
- WCMM-Wallenberg Centre for Molecular Medicine
- eSSENCE: The e-Science Collaboration
- Lund University Bioimaging Center
- Lung Biology (research group)
- publishing date
- 2023-02-03
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Pulmonary Circulation
- volume
- 13
- issue
- 1
- article number
- e12200
- publisher
- SAGE Publications
- external identifiers
-
- scopus:85152393186
- pmid:36824691
- ISSN
- 2045-8932
- DOI
- 10.1002/pul2.12200
- language
- English
- LU publication?
- yes
- additional info
- © 2023 The Authors. Pulmonary Circulation published by Wiley Periodicals LLC on behalf of the Pulmonary Vascular Research Institute.
- id
- 4dc0f180-8938-456d-a6b1-d5e1e31e2495
- date added to LUP
- 2023-02-25 19:50:12
- date last changed
- 2024-04-19 20:19:23
@article{4dc0f180-8938-456d-a6b1-d5e1e31e2495, abstract = {{<p>Expansion of extracellular matrix occurs in all stages of pulmonary angiopathy associated with pulmonary arterial hypertension (PAH). In systemic arteries, dysregulation and accumulation of the large chondroitin-sulfate proteoglycan aggrecan is associated with swelling and disruption of vessel wall homeostasis. Whether aggrecan is present in pulmonary arteries, and its potential roles in PAH, has not been thoroughly investigated. Here, lung tissue from 11 patients with idiopathic PAH was imaged using synchrotron radiation phase-contrast microcomputed tomography (TOMCAT beamline, Swiss Light Source). Immunohistochemistry for aggrecan core protein in subsequently sectioned lung tissue demonstrated accumulation in PAH compared with failed donor lung controls. RNAscope in situ hybridization indicated<br> ACAN expression in vascular endothelium and smooth muscle cells. Based on qualitative histological analysis, aggrecan localizes to cellular, rather than fibrotic or collagenous, lesions. Interestingly, <br> ADAMTS15, a potential aggrecanase, was upregulated in pulmonary arteries in PAH. Aligning traditional histological analysis with three-dimensional renderings of pulmonary arteries from synchrotron imaging identified aggrecan in lumen-reducing lesions containing loose, cell-rich connective tissue, at sites of intrapulmonary bronchopulmonary shunting, and at sites of presumed elevated pulmonary blood pressure. Our findings suggest that <br> ACAN expression may be an early response to injury in pulmonary angiopathy and supports recent work showing that dysregulation of aggrecan turnover is a hallmark of arterial adaptations to altered hemodynamics. Whether cause or effect, aggrecan and aggrecanase regulation in PAH are potential therapeutic targets.<br> </p>}}, author = {{van der Have, Oscar and Mead, Timothy J and Westöö, Christian and Peruzzi, Niccolò and Mutgan, Ayse C and Norvik, Christian and Bech, Martin and Struglics, André and Hoetzenecker, Konrad and Brunnström, Hans and Westergren-Thorsson, Gunilla and Kwapiszewska, Grazyna and Apte, Suneel S and Tran-Lundmark, Karin}}, issn = {{2045-8932}}, language = {{eng}}, month = {{02}}, number = {{1}}, publisher = {{SAGE Publications}}, series = {{Pulmonary Circulation}}, title = {{Aggrecan accumulates at sites of increased pulmonary arterial pressure in idiopathic pulmonary arterial hypertension}}, url = {{http://dx.doi.org/10.1002/pul2.12200}}, doi = {{10.1002/pul2.12200}}, volume = {{13}}, year = {{2023}}, }