Aerobic exercise reshapes arterial and macrophage gene expression toward atheroprotection in CETP-transgenic mice, independent of changes in CETP activity (Front Physiol 2018)

Original title: Exercise Training Favorably Modulates Gene and Protein Expression That Regulate Arterial Cholesterol Content in CETP Transgenic Mice

Front Physiol · 1 January 2018 · 6

Pinto PR, da Silva KS, Iborra RT, Okuda LS, Gomes-Kjerulf D, Ferreira GS, Machado-Lima A, Rocco DDFM, Nakandakare ER, Machado UF, Correa-Giannella ML, Catanozi S et al.

Three-month-old male cholesteryl ester transfer protein-transgenic (CETP-tg) mice underwent 6 weeks of aerobic exercise training or remained sedentary, with peritoneal macrophages and the aortic arch sampled immediately or 48 hours after the final session. Exercise training did not change body weight, plasma cholesterol, triglycerides, glucose, or CETP activity. Trained mice showed higher PPAR-gamma and ABCA-1 and lower MCP-1 and IL-10 gene expression in macrophages, and increased ABCA-1, SR-BI, and IL-6 with decreased LOX-1, MCP-1, TNF, and IL-10 gene expression in the aorta, with LOX-1 and MCP-1 remaining diminished at 48 hours and aortic LOX-1 protein confirmed reduced. Apolipoprotein A-I- and HDL2-mediated macrophage cholesterol efflux did not differ between groups. Exercise training therefore favorably modulates arterial and macrophage gene expression in the presence of CETP, independent of changes in CETP activity itself.

Original abstract

Aerobic exercise training (AET) improves the reverse cholesterol transport (RCT) in cholesteryl ester transfer protein-transgenic (CETP-tg) mice. We aimed at investigating the role of AET in the expression of genes and proteins involved in lipid flux in the aorta and macrophages of CETP-tg mice. Three-month-old male mice were randomly divided into trained (T; treadmill 15 m/min; 30 min/day) and sedentary (S) groups. After 6 weeks, peritoneal macrophages and the aortic arch were obtained immediately (0 h) or 48 h after the last exercise session. mRNA was determined by RT-qPCR, protein levels by immunoblot and 14C-cholesterol efflux determined in macrophages. AET did not change body weight, plasma cholesterol, triglycerides, glucose and CETP activity. In macrophages, at time 0 h, a higher expression of genes that encode PPAR gamma, ABCA-1 and a lower expression of MCP-1 and IL-10, was observed in T as compared to S. After 48 h, lower expressions of MCP-1 and PPAR gamma genes were observed in T mice. Increase in ABCA-1, SR-BI and IL-6 and decrease of LOX-1, MCP-1, TNF and IL-10 gene expression was observed in the aorta of T compared to S mice (0 h) and LOX-1 and MCP-1 remained diminished after 48 h. The protein level of MCP-1 and SR-BI in the aortic arch was unchanged in T animals after 48 h as compared to S, but LOX-1 was reduced confirming data of gene expression. The apo A-I and the HDL2 mediated-cholesterol efflux (8 and 24 h) were not different between T and S animals. In the presence of CETP, AET positively influences gene expression in the arterial wall and macrophages of CETP-tg mice contributing to the RCT and prevention of atherosclerosis. These changes were perceptible immediately after the exercise session and were influenced by the presence of CETP although independent of changes in its activity. Reductions in gene and protein expression of LOX-1 were parallel and reflect the ability of exercise training in reducing the uptake of modified LDL by the arterial wall macrophages.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.