title: Age-related changes in the contractile and passive arterial properties of murine mesenteric small arteries are altered by caveolin-1 knockout.
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.
authors.affiliation: Cardiovascular Research Group, University of Manchester, Manchester, UK.
authors.forename: Natasha
authors.initials: N
authors.lastname: Hausman
authors.forename: Julie
authors.initials: J
authors.lastname: Martin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Taggart
authors.forename: Clare
authors.initials: C
authors.lastname: Austin
mesh_terms: D000375:Aging / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D021941:Caveolae / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051242:Caveolin 1 / Q000172:deficiency* / Q000378:metabolism; D017353:Gene Deletion; D005838:Genotype; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009638:Norepinephrine / Q000494:pharmacology; D015203:Reproducibility of Results
chemical_list: D051242:Caveolin 1; D009638:Norepinephrine