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Cardiovasc Pathol. 2018 Jul - Aug;35:12-19. doi: 10.1016/j.carpath.2018.03.003. Epub 2018 Apr 7.

Thrombospondin-4 mediates cardiovascular remodelling in angiotensin II-induced hypertension.

Author information

1
Department of Biomedical Engineering & Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
2
Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Academic Medical Center, Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.
3
Department of Experimental Medical Science, Lund University, Lund, Sweden.
4
Electron Microscopy Center Amsterdam, Department of Medical Biology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
5
Department of Biomedical Engineering & Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: n.t.bakker@amc.uva.nl.

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 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.

KEYWORDS:

aortic dissection; heart hypertrophy; perivascular fibrosis; thrombospondin 4

PMID:
29729633
DOI:
10.1016/j.carpath.2018.03.003
[Indexed for MEDLINE]
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