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Lower extremity arteriosclerosis obliterans (LEASO) is a vascular disease that may result in adult limb loss worldwide. CD4[+]T cell-mediated immunity plays a significant role in LEASO. The T cell immunoglobulin and mucin domain 3 (Tim-3) and inhibitory receptor programmed cell death-1 (PD-1) are well-known immune checkpoints that play crucial roles in regulating CD4[+]T cell activation or tolerance. In this study, blood mononuclear cells were isolated from the blood samples of healthy controls and patients who were diagnosed with LEASO for the first time [stage III or IV according to the Fontaine classification system and had not received drugs (except for heparin) or surgery treatment]. We concluded the higher proportion of Tim-3[+]PD-1[+]CD4[+]T cells in human higher stage LEASO, and oxidized low-density lipoprotein increased Tim-3 and PD-1 co-expression by activating CD4[+]T cells in a dose- dependent manner. Tim-3[+]PD-1[+]CD4[+]T cells displayed a more active status and produced more anti-atherogenic cytokines compared to Tim-3[-]PD-1[-]CD4[+]T cells. Apart from the increased frequency, the altered function of Tim-3[+]PD-1[+]CD4[+]T cells was also observed in LEASO compared to those from healthy controls. These in vitro results indicated that Tim-3 and PD-1 might be promising early warning targets of higher stage LEASO. In addition, the blockade of Tim-3 and PD-1 signaling pathways aggravated the pro-atherogenic Th1 responses in LEASO, further suggesting that the cardiovascular safety must be a criterion considered in using immune checkpoint inhibitors to reverse T cell exhaustion during tumors and chronic viral infections.
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Objective: To observe the effects of high-flux haemodialysis (HFSD) on fibroblast growth factor 23 (FGF23) levels, calcium and phosphorus metabolism disorders, arteriosclerosis, and cardiac function in patients with end-stage renal disease (ESRD), and further clarify the advantages of HFSD in reducing the complications of ESRD. Methods: Sixty renal failure patients who underwent haemodialysis in our department of nephrology from October 2015 to October 2016 were randomly divided into the observation group and control group, with 30 cases in each group. The patients in the control group were given basic treatment and routine haemodialysis and the patients in the observation group underwent basic treatment and high-throughput haemodialysis. The changes in the FGF23 levels and the related indexes after two, four, and six months of treatment were observed. The carotid intima-media thickness (cIMT) and left ventricular ejection fraction (LVEF) before dialysis treatment and dialysis were observed. Results: After dialysis was completed, the serum P3+ concentration of the two groups was lower than that before treatment, and the serum Ca2+ concentration was negatively correlated with the P3+ concentration. In the second month of dialysis, the serum Ca2+ and P3+ concentrations in the two groups were not significantly changed. In the fourth and sixth months of dialysis, the serum P3+ concentration of the observation group was better than that of the control group, and the serum Ca2+ concentration was better than the control group, the difference was statistically significant (P<0.05). In the second, fourth, and sixth months of the dialysis, the serum FGF23 concentration in the observation group was significantly lower than that in the control group, which was statistically significant (P<0.05). The cIMT and LVEF were lower in both groups after dialysis, and the observation group was superior to the control group (P<0.05). Conclusion: In patients with ESRD, HFHD can eliminate FGF23, correct calcium and phosphorus metabolism disorders, improve arteriosclerosis, and can improve cardiac function.
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Introduction: Endothelial dysfunction is an early step in the atherosclerotic process and can be quantified by flow‐mediated vasodilation (FMD). Our aim was to investigate the effect of long‐term rosuvastatin therapy on endothelial function in patients with inflammatory joint diseases (IJD) with established atherosclerosis. Furthermore, to evaluate correlations between change in FMD (DELTAFMD) and change in carotid plaque (CP) height, arterial stiffness [aortic pulse wave velocity (aPWV) and augmentation index (AIx)], lipids, disease activity and inflammation. Methods: Eighty‐five statin‐naive patients with IJD and ultrasound‐verified CP (rheumatoid arthritis: n = 53, ankylosing spondylitis: n = 24, psoriatic arthritis: n = 8) received rosuvastatin treatment for 18 months. Paired‐samples t tests were used to assess DELTAFMD from baseline to study end. Linear regression models were applied to evaluate correlations between DELTAFMD and cardiovascular risk factors, rheumatic disease variables and medication. Results: The mean +/‐ SD FMD was significantly improved from 7.10 +/‐ 3.14 % at baseline to 8.70 +/‐ 2.98 % at study end (p < 0.001). Improvement in AIx (p < 0.05) and CP height reduction (p = 0.001) were significantly associated with DELTAFMD (dependent variable). Conclusions: Long‐term lipid lowering with rosuvastatin improved endothelial function in IJD patients with established atherosclerotic disease. Reduced arterial stiffness and CP regression were longitudinally correlated with the improvement in endothelial function measured by FMD. Trial registration: ClinicalTrials.gov NCT01389388. Registered 16 April 2010.
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