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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Academic Medical Center
  • University of Amsterdam
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Kardiologi
Originalspråkengelska
Sidor (från-till)H1486-H1493
TidskriftAmerican Journal of Physiology: Heart and Circulatory Physiology
Volym310
Utgivningsnummer11
StatusPublished - 2016
PublikationskategoriForskning
Peer review utfördJa