Exercise‐induced effects on atherogenesis and tryptophan catabolism via the kynurenine pathway in an HIV‐associated atherosclerosis mouse model

A mouse model of HIV‐associated atherosclerosis ( Tg26 +/− ApoE −/− ) exhibited increased plaque area compared with the ApoE −/− mouse, linked to elevated indoleamine 2,3‐dioxygenase (IDO) activity. IDO catalyses the conversion of tryptophan (TRP) into kynurenine (KYN), measured by the KYN‐to‐TRP ratio. As a biomarker of inflammation, IDO has been implicated as a risk factor for cardiovascular disease. To investigate the effect of exercise training on atherogenesis and IDO activity in Tg26 +/− ApoE −/− mice, nine Tg26 +/− ApoE −/− and 18 ApoE −/− male mice were fed an atherogenic diet and randomized into exercised or control groups. The exercised groups underwent an 8‐week treadmill protocol at moderate intensity (five times per week at 60% maximum velocity). Concentrations of KYN, TRP and cytokines were measured using ELISA, immune expression by flow cytometry, and lipid profile by a biochemistry analyser. Aortas were harvested post mortem for en face analysis. Tg26 +/− ApoE −/− mice showed ∼40% larger plaques than ApoE −/− mice ( P = 0.01), with slightly higher neutrophil ( P = 0.05) and monocyte expression ( P = 0.06). Plaque area was reduced by 40% in exercised ApoE −/− mice ( P = 0.04), but by only 12% in exercised Tg26 +/− ApoE −/− animals ( P = 0.85). Exercised Tg26 +/− ApoE −/− mice showed higher IDO activity than exercised ApoE −/− mice (58.57% ± 6.88% vs. −4.62% ± 17.20%, P = 0.01), which was positively correlated with plaque area ( R = 0.99, P = 0.02). Exercised ApoE − / − mice showed significantly lower triglyceride levels compared with exercised Tg26 +/− ApoE −/− mice (75.8 ± 14.8 vs. 165.2 ± 43.6 mg/dL; P = 0.02). Unlike ApoE −/− mice, moderate‐intensity aerobic training did not reduce plaque area in mice with HIV‐associated atherosclerosis. Moreover, exercise training appeared to increase inflammation in Tg26 +/− ApoE −/− mice, as indicated by elevated IDO activity.