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

Natasha Hausman, Julie Martin, Michael J Taggart, Clare Austin

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 properties. 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 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.

Original languageEnglish
Pages (from-to)1720-30
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume16
Issue number8
DOIs
Publication statusPublished - Aug 2012

Keywords

  • Aging/drug effects
  • Animals
  • Biomechanical Phenomena/drug effects
  • Caveolae/drug effects
  • Caveolin 1/deficiency
  • Gene Deletion
  • Genotype
  • In Vitro Techniques
  • Male
  • Mesenteric Arteries/drug effects
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Norepinephrine/pharmacology
  • Reproducibility of Results

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