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

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.

Novel Biomaterial for Artery Patch in Swine Model With High-Fat Diet

“…The 7-keto cholesterol, a typical biomarker of atherosclerosis, was also detected in both arterial and neo-vascular tissues in patch-angioplasties (Figures 7A-C, red). The ABCA (a lipometabolism-related protein) (Pinto et al, 2018) was expressed not only in arterial tissue but also in the neo-vascular tissue in patch-angioplasties (Figures 7D-F). PACK9 (a lipotransportation-related protein) (Elseweidy et al, 2019) was expressed in arterial tissue and the expression in neo-vascular tissue in patch-angioplasties was also robust (Figures 7G-I).…”

Physical activity to reduce PCSK9 levels

“…PCSK9 and LOX-1 are both involved in the atherosclerotic process ( 59 ) and recent evidence showed that PCSK9 and LOX-1 influence each other in the vascular tissue ( 18 , 60 ) and are co-related to the atheroma formation. Pre-clinical evidence showed that PA can reduce cholesterol accumulation in atherosclerotic plaques via the reduction of LOX-1 gene expression ( 61 ). Both PCSK9 and LOX-1 are reduced upon exercise ( 22 ).…”

Physical Activity and Alzheimer’s Disease: A Narrative Review

“…It should be emphasised that gene expression might be influenced by numerous environmental factors among them physical activity is the essential (major factor). A higher expression of certain genes (PPARG, NR1H3, ABCA1, ABCG1, CETP) has been observed even after of low-intensity exercise [47][48][49][50]. However, as to whether analogue process concerns genes involved in AD remains equivocal.…”