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.
Highlights
Cardiovascular diseases are responsible for considerable mortality and morbidity in the developed world and ageing is a clear risk factor for the development of such disorders [1]
The assignment of individual genotype based upon the above PCR expression profiles was confirmed in a subset of tissues wherein mice assigned by genotyping as caveolin-1 KO had, as anticipated, a complete absence of caveolin-1 protein in contrast to WT animals (Fig. 1C)
Whilst electron micrographs of arteries from WT arteries confirmed the presence of caveolae, there was no evidence of caveolae in arteries from caveolin-1 KO mice (Figs 2 and 3)
Summary
Cardiovascular diseases are responsible for considerable mortality and morbidity in the developed world and ageing is a clear risk factor for the development of such disorders [1]. Caveolin-1 has been long known to be a protein integral to caveolae formation and caveolin-1 knockout mice (caveolin-1 KO) lack identifiable caveolae in the vasculature [12, 14, 15]. These mice are viable and fertile they exhibit reductions in lifespan which suggests a role for caveolin-1 and/or caveolae in the ageing doi:10.1111/j.1582-4934.2011.01457.x
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