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X-ray Phase-contrast imaging

Martin Bech

Universitetslektor

X-ray Phase-contrast imaging

Aggrecan accumulates at sites of increased pulmonary arterial pressure in idiopathic pulmonary arterial hypertension

Författare

  • Oscar van der Have
  • Timothy J Mead
  • Christian Westöö
  • Niccolò Peruzzi
  • Ayse C Mutgan
  • Christian Norvik
  • Martin Bech
  • André Struglics
  • Konrad Hoetzenecker
  • Hans Brunnström
  • Gunilla Westergren-Thorsson
  • Grazyna Kwapiszewska
  • Suneel S Apte
  • Karin Tran-Lundmark

Summary, in English

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
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.

Avdelning/ar

  • Kärlväggsbiologi
  • Medicinsk strålningsfysik, Lund
  • LTH profilområde: Teknik för hälsa
  • X-ray Phase Contrast
  • Lund OsteoArthritis Division - Nedbrytning av ledbrosk: en biologisk process som leder till artros
  • LUCC: Lunds universitets cancercentrum
  • Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga
  • WCMM- Wallenberg center för molekylär medicinsk forskning
  • eSSENCE: The e-Science Collaboration
  • Lund University Bioimaging Center
  • Lungbiologi

Publiceringsår

2023-02-03

Språk

Engelska

Publikation/Tidskrift/Serie

Pulmonary Circulation

Volym

13

Issue

1

Dokumenttyp

Artikel i tidskrift

Förlag

SAGE Publications

Ämne

  • Cell and Molecular Biology

Status

Published

Forskningsgrupp

  • Vessel Wall Biology
  • X-ray Phase Contrast
  • Lund OsteoArthritis Division - Molecular marker research group
  • Improved diagnostics and prognostics of lung cancer and metastases to the lungs
  • Lung Biology

ISBN/ISSN/Övrigt

  • ISSN: 2045-8932