Thrombospondin-4 mediates cardiovascular remodelling in angiotensin II-induced hypertension
(2018) In Cardiovascular Pathology 35. p.12-19- Abstract
Thrombospondin 4 (TSP-4) expression is induced in the heart and vasculature under pathological conditions, including myocardial infarction, myocardial pressure overload, and hypertension. TSP-4 is linked to remodelling processes, where it may affect extracellular matrix protein organization. In previous work, we studied the role of TSP-4 in small arteries during hypertension using Ang II-treated Thrombospondin 4 knockout (Thbs4−/−) mice. We reported increased heart weight, as well as the occurrence of aortic aneurysms in the Ang II-treated Thbs4−/− animals. In the present study, we further characterized the hearts and aortas from these animals. Hypertrophy of cardiomyocytes, together with perivascular fibrosis and... (More)
Thrombospondin 4 (TSP-4) expression is induced in the heart and vasculature under pathological conditions, including myocardial infarction, myocardial pressure overload, and hypertension. TSP-4 is linked to remodelling processes, where it may affect extracellular matrix protein organization. In previous work, we studied the role of TSP-4 in small arteries during hypertension using Ang II-treated Thrombospondin 4 knockout (Thbs4−/−) mice. We reported increased heart weight, as well as the occurrence of aortic aneurysms in the Ang II-treated Thbs4−/− animals. In the present study, we further characterized the hearts and aortas from these animals. Hypertrophy of cardiomyocytes, together with perivascular fibrosis and inflammation was observed in the Ang II-treated Thbs4−/− hearts. In the aortas, an increase in the aortic wall cross-sectional area (CSA) and wall thickness of the Ang II-treated Thbs4−/− mice was found. More detailed investigation of the Ang II-treated Thbs4−/− aortas also revealed the appearance of aortic dissections in the outer medial layer of the arteries, as well as pronounced inflammation. No differences were found in several other extracellular matrix-related parameters, such as number of elastin breaks or stress–strain relationships. However, at the ultrastructural level, collagen fibers showed alterations in diameter in the media and adventitia of the Ang II-treated Thbs4−/− mice, in the area prone to dissection. In conclusion, we identified TSP-4 as an important protein in the development of cardiac hypertrophy and aortic dissections in Ang II-induced hypertension.
(Less)
- author
- organization
- publishing date
- 2018-07-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- aortic dissection, heart hypertrophy, perivascular fibrosis, thrombospondin 4
- in
- Cardiovascular Pathology
- volume
- 35
- pages
- 8 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:29729633
- scopus:85046790264
- ISSN
- 1054-8807
- DOI
- 10.1016/j.carpath.2018.03.003
- language
- English
- LU publication?
- yes
- id
- b969ce60-6989-4f64-8c6c-5b219c9100d5
- date added to LUP
- 2018-05-21 14:47:41
- date last changed
- 2024-10-30 03:19:20
@article{b969ce60-6989-4f64-8c6c-5b219c9100d5,
abstract = {{<p>Thrombospondin 4 (TSP-4) expression is induced in the heart and vasculature under pathological conditions, including myocardial infarction, myocardial pressure overload, and hypertension. TSP-4 is linked to remodelling processes, where it may affect extracellular matrix protein organization. In previous work, we studied the role of TSP-4 in small arteries during hypertension using Ang II-treated Thrombospondin 4 knockout (Thbs4<sup>−/−</sup>) mice. We reported increased heart weight, as well as the occurrence of aortic aneurysms in the Ang II-treated Thbs4<sup>−/−</sup> animals. In the present study, we further characterized the hearts and aortas from these animals. Hypertrophy of cardiomyocytes, together with perivascular fibrosis and inflammation was observed in the Ang II-treated Thbs4<sup>−/−</sup> hearts. In the aortas, an increase in the aortic wall cross-sectional area (CSA) and wall thickness of the Ang II-treated Thbs4<sup>−/−</sup> mice was found. More detailed investigation of the Ang II-treated Thbs4<sup>−/−</sup> aortas also revealed the appearance of aortic dissections in the outer medial layer of the arteries, as well as pronounced inflammation. No differences were found in several other extracellular matrix-related parameters, such as number of elastin breaks or stress–strain relationships. However, at the ultrastructural level, collagen fibers showed alterations in diameter in the media and adventitia of the Ang II-treated Thbs4<sup>−/−</sup> mice, in the area prone to dissection. In conclusion, we identified TSP-4 as an important protein in the development of cardiac hypertrophy and aortic dissections in Ang II-induced hypertension.</p>}},
author = {{Palao, Teresa and Medzikovic, Lejla and Rippe, Catarina and Wanga, Shaynah and Al-Mardini, Claudia and van Weert, Angela and de Vos, Judith and van der Wel, Nicole N. and van Veen, Henk A. and van Bavel, Ed T. and Swärd, Karl and de Waard, Vivian and Bakker, Erik NTP}},
issn = {{1054-8807}},
keywords = {{aortic dissection; heart hypertrophy; perivascular fibrosis; thrombospondin 4}},
language = {{eng}},
month = {{07}},
pages = {{12--19}},
publisher = {{Elsevier}},
series = {{Cardiovascular Pathology}},
title = {{Thrombospondin-4 mediates cardiovascular remodelling in angiotensin II-induced hypertension}},
url = {{http://dx.doi.org/10.1016/j.carpath.2018.03.003}},
doi = {{10.1016/j.carpath.2018.03.003}},
volume = {{35}},
year = {{2018}},
}