212 Effects of perivascular adipose tissue and high fat feeding on vascular reactivity in the apoe–/–mouse

Abstract

Perivascular adipose tissue (PVAT) surrounds the majority of blood vessels and has recently been suggested to play a role in the pathogenesis of atherosclerosis. PVAT exerts anti-contractile effects that are abolished in disease states, these effects could potentially modulate atherosclerosis. The aims of this study were to determine the influence of PVAT, age, high fat diet (HFD) and associated progression of atherosclerosis on isolated arterial reactivity. Male ApoE -/- mice were fed a high fat or standard chow diet for 8, 16 or 26 weeks. Aortic atherosclerotic lesion areas were analysed by en face quantification with Oil Red O. Contractile responses of thoracic aortae to cumulative doses of phenylephrine (1 × 10 –10 – 3 × 10 –5 M) or a maximal dose of serotonin (1 × 10 –5 M) were measured in PVAT intact or denuded vessels using myography. Endothelial function was evaluated by relaxation to acetylcholine (1 × 10 –5 M) on vessels pre-constricted with phenylephrine (1 × 10 –5 M). High fat feeding significantly increased the percentage of aortic area covered by atherosclerotic lesions in the ApoE -/- mouse at each time-point (standard chow versus HFD; 8 weeks: 0.11%±0.08 vs. 1.53% ± 0.21; 16 weeks: 1.28%±0.08 vs. 8.89%±0.80; 26 weeks: 2.79%±0.85 vs. 25.43%±2.65). PVAT significantly increased vasoconstrictor responses to phenylephrine at the 8 and 16 week time-points in HFD fed and age-matched controls (8 week chow: PVAT versus no PVAT P = 0.006, n = 12. 8 week HFD: PVAT versus no PVAT, P = 0.03, n = 10, 16 week chow: PVAT versus no PVAT P = 0.0001, n = 11. 16 week HFD: PVAT versus no PVAT, P = 0.004, n = 9). PVAT exerted anti-contractile effects in the 26 week controls (PVAT versus no PVAT P = 0.02, n = 7). PVAT exerted no effect on vessel contractility in the 26 week HFD group (HFD: PVAT versus no PVAT P=NS, n = 9). Contractile responses to serotonin were unaffected by atherosclerotic progression or the presence of PVAT. Endothelial dysfunction was observed in the 26 week chow cohort however, this was not demonstrated in the HFD groups. PVAT exerted no effect on aortic relaxation. In summary, PVAT modulated the vasoconstrictor responses of aortic segments to phenylephrine during atherosclerotic disease progression in the ApoE –/– mouse. However, relaxation in response to acetylcholine, an endothelium-dependent vasodilator, was not significantly altered by the presence of PVAT. These findings may have important implications in the pathogenesis of atherosclerosis. This research was funded by the British Heart Foundation.