Senescence-induced remodelling in large and small arteries of mice: impact of high-fat diet.

Aging and weight gain are independent cardiovascular risk factors, which have shown to be increasingly associated. We hypothesize that high-fat intake could lead to arterial remodelling similar to that promoted by vascular aging and worsen the remodelling exerted by senescence. For this purpose we analysed structure of large (aorta) and small (mesenteric artery, MA) arteries from senescence accelerated mice (SAM) following a Western-type diet (WD; 21 % fat). Five-month-old SAM prone (SAMP8) and resistant (SAMR1) female mice were fed a WD for 8 weeks. At 7 months of age, aortas and MAs were dissected. In aorta, vascular structure and mature or newly synthesized collagen was analysed by morphometric analysis of haematoxylin and eosin-stained cross sections and picrosirius red, respectively. In MA, vascular structure, collagen I/III protein and mRNA expression, and nuclei distribution was evaluated by pressure myography, immunofluores-cence, RT-qPCR and confocal microscopy, respectively. Values are means ± S.E.M. compared by two way ANOVA with Bonferroni's post-test. On normal chow, weight gain, abdominal fat and cholesterol levels were comparable between strains and similarly increased after WD (Jiménez-Altayó etal., 2012). In aorta, wall thickness (WT), but not cross sectional area (CSA), was increased by senescence (SAMR1: 171.3±4.8 μm, n=7; SAMP8: 194.6±6.1 μm, n=8, p<0.05). WD only modified aortic structure in SAMR1 (control: 171.3±4.8 μm, n=7; WD: 209.8±10.0 μm, n=7, p<0.01) paralleled by an increase in mature (n=11) and newly synthesized (n=9) collagen. In MAs, senescence did not alter the wall/lumen ratio but diminished (p<0.05) the CSA and WT in association with reduced number of adventitial (SAMR1: 2339±194, n=6; SAMP8:1145±81, n=3, p<0.01) and smooth muscle (SAMR1: 3535±213, n=6; SAMP8l:2613±68, n=3, p<0.05) cells per mm³. WD decreased MA CSA (p<0.01), WT (p<0.001) and wall/lumen ratio (p<0.05) in SAMR1 paralleled by diminished adventitial (control: 2339±194, n=6; WD: 1393±269, n=6, p<0.05) and smooth muscle (control: 3535±213, n=6; WD: 2314±230, n=6, p<0.01) cells per mm³. Nevertheless, WD intake in SAMP8 did notfurther modify MA structure. Collagen I/III protein (n=4-6) and mRNA expression (n=4-6) was unaltered by senescence or diet. Therefore, senescence induces qualitatively different remodelling in large and small arteries of mice. High-fat intake promotes remodelling in non-senescent mice consistent with accelerated senescence, whereas the vasculature of senescent mice does not display any further alteration. In both cases, arterial remodelling may exacerbate vascular injury. [ABSTRACT FROM AUTHOR]