BACKGROUND: 5-Methoxytryptophan (5-MTP), a new endothelial factor with vasoprotective and anti-inflammatory effects, reduces aortic chondrogenesis and calcification during atherosclerosis. The aim of this study was to investigate the effects of aerobic exercise on aortic chondrogenesis and calcification during atherosclerosis in rats. To investigate the effect of aerobic exercise on the expression of 5-MTP/P38 MAPK signaling pathway. To lay a theoretical foundation for the therapeutic effect of exercise in rat atherosclerosis model. METHODS: Establishment of a rat model of atherosclerosis using a high-fat diet combined with intraperitoneal injection of vitamin D3 (VD3). The aerobic exercise group underwent moderate-intensity aerobic exercise on an exercise treadmill for 8 weeks, while the atherosclerosis model group and the control group did not exercise. After exercise, blood and aortic samples were collected from all rats to evaluate the levels of serum triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDLC), aortic chondrogenesis, calcification, 5-MTP level, collagen II, P38MAPK, pp38 MAPK, and IL-6 protein content. RESULTS: (1)8 weeks of aerobic exercise significantly reduced aortic chondrogenesis, area of calcification, serum LDL-C, TC levels, atherosclerotic index and serum IL-6 levels in rats (p <
0.01), and lowered TG levels (p <
0.05)
(2)8 weeks of aerobic exercise significantly increased aortic 5-MTP levels (p <
0.01) and decreased the content of aortic pp38MAPK, collagen II and IL-6 proteins significantly (p <
0.01). The pp38MAPK/P38MAPK ratio was also decreased (p <
0.01). CONCLUSION: 8 weeks of aerobic exercise training improved dyslipidemia and reduced aortic chondrogenesis and calcification formation in AS rats. The mechanism may be related to increasing aortic 5-MTP levels and inhibiting the P38MAPK/ IL-6 signaling pathway.