The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

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

På svenska

Author

Summary, in English

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.

Publishing year

2016

Language

English

Pages

1486-1493

Publication/Series

American Journal of Physiology: Heart and Circulatory Physiology

Volume

310

Issue

11

Document type

Journal article

Publisher

American Physiological Society

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cellular Biomechanics

ISBN/ISSN/Other

  • ISSN: 1522-1539