Thrombospondin-4 knockout in hypertension protects small artery endothelial function but induces aortic aneurysms.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8852653
- author
- Palao, Teresa ; Rippe, Catarina LU ; van Veen, Henk A ; VanBavel, Ed ; Swärd, Karl LU and Bakker, Erik N
- organization
- publishing date
- 2016
- type
- 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
- 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
- 2016-04-01 10:43:35
- date last changed
- 2022-04-04 20:44:35
@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}}, doi = {{10.1152/ajpheart.00046.2016}}, volume = {{310}}, year = {{2016}}, }