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Thrombospondin-4 knockout in hypertension protects small artery endothelial function but induces aortic aneurysms.

Palao, Teresa; Rippe, Catarina LU ; van Veen, Henk A; VanBavel, Ed; Swärd, Karl LU and Bakker, Erik N (2016) In American Journal of Physiology: Heart and Circulatory Physiology 310(11). p.1486-1493
Abstract
Thrombospondin-4 (TSP-4) is a multidomain calcium-binding protein that has both intracellular and extracellular functions. As an extracellular matrix protein it is involved in remodeling processes. Previous work showed that in the cardiovascular system, TSP-4 expression is induced in the heart in response to experimental pressure overload and infarction injury. Intracellularly, it mediates the endoplasmic reticulum (ER) stress response in the heart. In this study we explored the role of TSP-4 in hypertension. For this purpose, wild type (WT) and thrombospondin-4 knockout (Thbs4(-/-)) mice were treated with angiotensin II (Ang II). Hearts from Ang II-treated Thbs4(-/-) mice showed an exaggerated hypertrophic response. Interestingly, aortas... (More)
Thrombospondin-4 (TSP-4) is a multidomain calcium-binding protein that has both intracellular and extracellular functions. As an extracellular matrix protein it is involved in remodeling processes. Previous work showed that in the cardiovascular system, TSP-4 expression is induced in the heart in response to experimental pressure overload and infarction injury. Intracellularly, it mediates the endoplasmic reticulum (ER) stress response in the heart. In this study we explored the role of TSP-4 in hypertension. For this purpose, wild type (WT) and thrombospondin-4 knockout (Thbs4(-/-)) mice were treated with angiotensin II (Ang II). Hearts from Ang II-treated Thbs4(-/-) mice showed an exaggerated hypertrophic response. Interestingly, aortas from Thbs4(-/-) mice treated with Ang II showed a high incidence of aneurysms. In resistance arteries, Ang II-treated WT mice showed impaired endothelial dependent relaxation. This was not observed in Ang II-treated Thbs4(-/-) mice or in untreated controls. No differences were found in the passive pressure-diameter curves or stress-strain relationships, although Ang II-treated Thbs4(-/-) mice showed a tendency to be less stiff, associated with thicker diameters of the collagen fibers as revealed by electron microscopy. We conclude that TSP-4 plays a role in hypertension, affecting cardiac hypertrophy, aortic aneurysm formation, as well as endothelial dependent relaxation in resistance arteries. (Less)
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organization
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Contribution to journal
publication status
published
subject
in
American Journal of Physiology: Heart and Circulatory Physiology
volume
310
issue
11
pages
1486 - 1493
publisher
American Physiological Society
external identifiers
  • pmid:26968543
  • scopus:84983760976
  • wos:000377434400012
ISSN
1522-1539
DOI
10.1152/ajpheart.00046.2016
language
English
LU publication?
yes
id
d53410f7-3c38-49c0-ba9e-5d754408e771 (old id 8852653)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26968543?dopt=Abstract
date added to LUP
2016-03-16 15:44:21
date last changed
2017-09-17 03:54:46
@article{d53410f7-3c38-49c0-ba9e-5d754408e771,
  abstract     = {Thrombospondin-4 (TSP-4) is a multidomain calcium-binding protein that has both intracellular and extracellular functions. As an extracellular matrix protein it is involved in remodeling processes. Previous work showed that in the cardiovascular system, TSP-4 expression is induced in the heart in response to experimental pressure overload and infarction injury. Intracellularly, it mediates the endoplasmic reticulum (ER) stress response in the heart. In this study we explored the role of TSP-4 in hypertension. For this purpose, wild type (WT) and thrombospondin-4 knockout (Thbs4(-/-)) mice were treated with angiotensin II (Ang II). Hearts from Ang II-treated Thbs4(-/-) mice showed an exaggerated hypertrophic response. Interestingly, aortas from Thbs4(-/-) mice treated with Ang II showed a high incidence of aneurysms. In resistance arteries, Ang II-treated WT mice showed impaired endothelial dependent relaxation. This was not observed in Ang II-treated Thbs4(-/-) mice or in untreated controls. No differences were found in the passive pressure-diameter curves or stress-strain relationships, although Ang II-treated Thbs4(-/-) mice showed a tendency to be less stiff, associated with thicker diameters of the collagen fibers as revealed by electron microscopy. We conclude that TSP-4 plays a role in hypertension, affecting cardiac hypertrophy, aortic aneurysm formation, as well as endothelial dependent relaxation in resistance arteries.},
  author       = {Palao, Teresa and Rippe, Catarina and van Veen, Henk A and VanBavel, Ed and Swärd, Karl and Bakker, Erik N},
  issn         = {1522-1539},
  language     = {eng},
  number       = {11},
  pages        = {1486--1493},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Heart and Circulatory Physiology},
  title        = {Thrombospondin-4 knockout in hypertension protects small artery endothelial function but induces aortic aneurysms.},
  url          = {http://dx.doi.org/10.1152/ajpheart.00046.2016},
  volume       = {310},
  year         = {2016},
}