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Thromb Haemost 2013; 110(04): 785-794
DOI: 10.1160/TH13-01-0022
Endothelium and Vascular Development
Schattauer GmbH

Age-associated pro-inflammatory adaptations of the mouse thoracic aorta

Bianca Hemmeryckx
1   Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium
,
Marc F. Hoylaerts
1   Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium
,
Eveline Deloose
1   Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium
3   Present address: Translational Research in Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
,
Cor E. Van Hove
2   Division of Pharmacology, Universiteit Antwerpen, Wilrijk, Belgium
,
Paul Fransen
2   Division of Pharmacology, Universiteit Antwerpen, Wilrijk, Belgium
,
Hidde Bult
2   Division of Pharmacology, Universiteit Antwerpen, Wilrijk, Belgium
,
H. Roger Lijnen
1   Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium
› Author Affiliations Financial Support: The Center for Molecular and Vascular Biology is supported by the “Programmafinanciering Katholieke Universiteit Leuven” (PF/10/014). This study was supported by FWO project G.0678.10.
Further Information

Publication History

Received: 10 January 2013

Accepted after major revision: 03 July 2013

Publication Date:
01 December 2017 (online)

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Summary

Arterial ageing may be associated with a reduction in vasodilation due to increased reactive oxygen species (ROS) production, whereas endothelial cell activation induces procoagulant changes. However, little is known on the effect of ageing on expression of anticoagulant endothelial markers such as endothelial protein C receptor (EPCR). To study age-associated alterations in smooth muscle cell (SMC) and endothelial cell (EC) structure and function, the aorta was isolated from 10-week-and 12– and 24-month-old C57BL/6J mice and analysed for its expression of genes involved in senescence, oxidative stress production, coagulation and matrix remodelling. In addition, vasorelaxation experiments were performed using 10-week-and 24-month-old thoracic aortic ring segments in organ chamber baths. The media thickness of the thoracic aorta progressively increased with age, associated with hypertrophy of vascular SMCs. Basal nitric oxide production and sensitivity to acetylcholine-mediated vasodilation in thoracic aorta rings was reduced with age, whereas no significant differences in ROS production could be demonstrated. Gene expression of tissue factor, EPCR and von Willebrand factor was not affected by ageing of the aorta, whereas that of thrombomodulin was mildly reduced and that of xanthine dehydrogenase, NADPH oxidase 4, tumour necrosis factor-α and vascular cell adhesion molecule-1 significantly enhanced. In conclusion, a reduction in endothelial cell-mediated vasodilation in aged thoracic aortas of C57BL/6J mice was accompanied by a shift towards a pro-inflammatory state of the endothelium.

Keywords

Vascular ageing - C57BL/6J mice - endothelial dysfunction - EPCR
 

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