Advanced

Versican accumulates in vascular lesions in pulmonary arterial hypertension

Chang, Ya Ting; Chan, Christina K.; Eriksson, Inger; Johnson, Pamela Y.; Cao, Xiaofang; Westöö, Christian; Norvik, Christian; Andersson-Sjöland, Annika LU ; Westergren-Thorsson, Gunilla LU and Johansson, Staffan, et al. (2016) In Pulmonary Circulation 6(3). p.347-359
Abstract

Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart... (More)

Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [35S]sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminogly-cans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Hypoxia, Mechanical strain, Pulmonary arterial hypertension, Vascular smooth-muscle cell, Versican
in
Pulmonary Circulation
volume
6
issue
3
pages
13 pages
publisher
University of Chicago Press
external identifiers
  • scopus:84987606120
  • wos:000383018300012
ISSN
2045-8932
DOI
10.1086/686994
language
English
LU publication?
yes
id
b4765a5d-6f4b-4ccc-805e-d0e4d86f2003
date added to LUP
2016-10-06 09:25:42
date last changed
2017-01-06 03:00:01
@article{b4765a5d-6f4b-4ccc-805e-d0e4d86f2003,
  abstract     = {<p>Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [<sup>35</sup>S]sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminogly-cans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH.</p>},
  author       = {Chang, Ya Ting and Chan, Christina K. and Eriksson, Inger and Johnson, Pamela Y. and Cao, Xiaofang and Westöö, Christian and Norvik, Christian and Andersson-Sjöland, Annika and Westergren-Thorsson, Gunilla and Johansson, Staffan and Hedin, Ulf and Kjellén, Lena and Wight, Thomas N. and Tran-Lundmark, Karin},
  issn         = {2045-8932},
  keyword      = {Hypoxia,Mechanical strain,Pulmonary arterial hypertension,Vascular smooth-muscle cell,Versican},
  language     = {eng},
  month        = {09},
  number       = {3},
  pages        = {347--359},
  publisher    = {University of Chicago Press},
  series       = {Pulmonary Circulation},
  title        = {Versican accumulates in vascular lesions in pulmonary arterial hypertension},
  url          = {http://dx.doi.org/10.1086/686994},
  volume       = {6},
  year         = {2016},
}