Objective To investigate the effects of uremic toxins (UT) on the inflammatory response and progression of coronary heart disease (CHD) by promoting monocyte senescence.

Methods An animal model was established using Sprague-Dawley (SD) rats. Thirty male rats were randomly divided into the control group, UT group and UT + Aspirin group, with 10 rats in each group. The UT group and UT + Aspirin group were administered gastric adenine, while those in the UT + Aspirin group were also administered gastric Aspirin simultaneously. After 8 weeks of drug administration intervention, the peripheral blood mononuclear cells of rats were isolated and cultured. The senescence level of cells was detected by β-gal staining. The expressions of senescence markers p16 and p21 were detected by Western blot. The levels of IL-6 and TNF-α secreted by cells were detected by ELISA. The pathological changes of myocardial tissue in rats were observed by HE and Masson staining, and the expression levels of cardiac inflammatory factors were detected by immunohistochemistry.

Results The experimental results indicated that UT treatment significantly increased the senescence level of monocytes in rats, and manifested as an increase in the proportion of β-gal positive cells and a significant upregulation of the expression levels of p16 and p21 proteins. In addition, the secretion level of pro-inflammatory factors in peripheral blood mononuclear cells of rats in the UT treatment group increased. The results of myocardial histopathological and immunohistochemical tests showed that UT treatment led to the thickening of coronary artery intima, swelling of myocardial cells and increasing of fibrosis and infiltration levels of inflammatory cells. However, in the UT + Aspirin group, these changes were significantly alleviated.

Conclusions UT can induce monocyte senescence in rats, leading to enhanced inflammatory responses and vascular endothelial dysfunction, which may aggravate the progression of CHD.