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Age-related changes in the contractile and passive arterial properties of murine mesenteric small arteries are altered by caveolin-1 knockout

Lookup NU author(s): Julie Taggart, Emeritus Professor Michael TaggartORCiD

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Abstract

Caveolin-1, an integral protein of caveolae, is associated with multiple cardiovascular signalling pathways. Caveolin-1 knockout (KO) mice have a reduced lifespan. As changes in artery structure and function are associated with ageing we have investigated the role of caveolin-1 ablation on age-related changes of small artery contractility and passive mechanical propertes. Mesenteric small arteries isolated from 3 and 12 month wild type (WT) and caveolin-1 KO mice were mounted on a pressure myograph and changes in passive and functional arterial properties were continuously monitored. In WT mice ageing was associated with a reduction in arterial contractility to noradrenaline which was reversed by inhibition of nitric oxide synthase (NOS) with L-NNA. Similarly, in 3 month old mice, caveolin-1 KO reduced contractility to noradrenaline by an L-NNA-sensitive mechanism. However, ageing in caveolin-1 KO mice was not associated with any further change in contractility. In WT mice ageing was associated with an increased passive arterial diameter and cross-sectional area (CSA), consistent with outward remodelling of the arterial wall, and a reduced arterial distensibility. Caveolin-1 ablation at 3 months of age resulted in similar changes in passive arterial properties to those observed with ageing in WT animals. However, ageing in caveolin-1 KO mice resulted in a reduced arterial CSA indicating different effects on passive structural characteristics from that observed in WT mice. Thus, caveolin-1 mice show abnormalities of small mesenteric artery function and passive mechanical characteristics indicative of premature vascular ageing. Moreover, caveolin-1 ablation modulates the age-related changes usually observed in mesenteric arteries of WT mice.

Publication metadata

Author(s): Hausman N, Martin J, Taggart MJ, Austin C

Publication type: Article

Publication status: Published

Journal: Journal of Cellular and Molecular Medicine

Year: 2012

Volume: 16

Issue: 8

Pages: 1720-1730

Print publication date: 29/07/2012

ISSN (print): 1582-1838

ISSN (electronic): 1582-4934

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1111/j.1582-4934.2011.01457.x

DOI: 10.1111/j.1582-4934.2011.01457.x

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