Author(s): GAO, Y., LU, J., ZHANG, L., XIANG, M., YUAN, X., SUN, W., XU, Y., XIAO, H., ZHANG, Y., TANG, Q., Institution: NANJING SPORT INSTITUTE, Country: CHINA, Abstract-ID: 1286

INTRODUCTION:
Type 2 diabetes mellitus (T2DM) could promote the course of hypercholesterolemia induced atherosclerosis in clinic. Researches have showed chronic hyperglycaemia leaded to glycation reaction generating such as advanced glycated end products (AGEs), which might exacerbate the atherosclerotic plaques through disrupting endothelial function. Aerobic exercise is an important prevention of cardiovascular and metabolic diseases. Consequently, in this work we aim to explore the mechanism of aerobic exercise improves atherosclerosis induced by hypercholesterolemia and hyperglycaemia.
METHODS:
Specific pathogen-free ApoE-/- (n=45) male mice were provided a high-fat diet containing 1.25% cholesterol and were subjected to intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) or sodium citrate buffer for 3 consecutive days to induce T2DM and were randomly divided into the following three groups: ApoE-/-, ApoE-/-+STZ and ApoE-/-+STZ+EX. Mice in ApoE-/-+STZ+EX group ran on a treadmill for 8 weeks (5 days/week, 40-60 min/day, 15 m/min). The levels of glucose and lipid in plasma were measured by biochemical analyzer. Levels of nitric oxide (NO) and AGEs were determined by ELISA kits. Oil red O staining was performed to evaluate the formation of aortic plaque.
RESULTS:
1) T2DM worse blood lipid, endothelial function and atherosclerosis in ApoE-/- mice. Injection of STZ aggravated the serum levels of TC (19.92±1.16vs27.90±0.78mmol/L, p<0.001), LDL-C (11.24±0.93vs16.15±0.52mmol/L, p<0.05). T2DM also increased AGEs (626.00±25.10vs874.40±11.45pg/mL, p<0.001) and impaired NO (33.62±2.82vs25.28±1.38μmol/L, p<0.05). Mice in ApoE-/-+STZ group had considerably larger plaque areas than ApoE-/- mice in both the total aorta (11.28%±0.81%vs16.39%±0.17%, p<0.01) and aortic roots (3.30%±0.40%vs6.52%±0.68%, p<0.01).
2) Aerobic exercise improves atherosclerosis and endothelial function through amelioration of AGEs. No significant difference in serum lipid biochemical markers were observed after training. The expression of NO (25.28±1.38vs42.51±1.12μmol/L, p<0.001) was elevated while the AGEs (874.40±11.45vs653.10±8.84pg/mL, p<0.001) production in plasma was inhibited remarkedly by exercise. Compared with the ApoE-/-+STZ group, the proportion of aortic plaque areas of the ApoE-/-+STZ +EX group was proved to be down-regulated (16.39%±0.17%vs11.87%±0.93%, p<0.01, 6.52%±0.68%vs3.67%±0.23%, p<0.05).
CONCLUSION:
T2DM aggravated hypercholesterolemia and impaired endothelial function through AGEs, which exacerbated atherosclerosis; Aerobic exercise did not ameliorate hypercholesterolemia, but attenuated atherosclerosis by improving endothelial function.