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Peritoneal dialysis (PD)-related peritoneal fibrosis (PF) is characterized by progressive extracellular matrix (ECM) accumulation in peritoneal mesothelial cells (PMCs) during long-term use of high glucose (HG)-based dialysates. Activation of the renin-angiotensin system (RAS) has been shown to be associated with PF. The aim of this study was to explore the underlying mechanism of the RAS in HG-induced PF. We treated C57BL/6 mice and a human PMC line with HG to induce a PF model and to stimulate ECM accumulation, respectively. RAS activity was blocked using valsartan or angiotensin II (ANGII) type 1 receptor siRNA. The major findings were as follows. First, mice in the HG group exhibited increased collagen deposition and expression of ECM proteins, including a-smooth muscle actin (a-SMA) and collagen type I in the peritoneum. Consistent with the in vivo data, HG upregulated a-SMA expression in human peritoneal mesothelial cells (HPMCs) in a time- and dose-dependent manner. Second, HG stimulation led to RAS activation in HPMCs, and inactivation of RAS decreased the expression of ECM proteins in vivo and in vitro, even during HG stimulation. Finally, RAS-mediated ECM production was associated with lipid accumulation in HPMCs and depended on the dysregulation of the low-density lipoprotein receptor (LDLr) pathway. HG-stimulated HPMCs showed increased coexpression of LDLr and α-SMA, whereas blockade of RAS activity reversed the effect. Furthermore, inhibition of LDLr signaling decreased α-SMA and collagen type I expression in HPMCs when treated with HG and ANG II. In conclusion, increased intracellular RAS activity impaired lipid homeostasis and induced ECM accumulation in HPMCs by disrupting the LDLr pathway, which contributed to PF. [ABSTRACT FROM AUTHOR]

Objective: To determine the impact of pulmonary hypertension (PH) on maintenance hemodialysis (MHD) patients' cardiovascular events and all-cause mortality. Methods: We included 90 MHD patients, divided into group with PH and group without PH. All patients had been followed up for 4 years, and the primary endpoints were all cause mortality and cardiovascular events. We compared the clinical data and the endpoint events between the two groups. Results: We found PH in 37 patients (41.11%). The incidence of previous cardiovascular disease in group with PH was significantly higher than that in group without PH (X2=2.034, P < 0.05). The left atrial diameter in group with PH was significantly higher than that in group without PH (t = 7.265, P < 0.01). Logistic regression analysis revealed that previous cardiovascular disease and left atrial diameter were the independent determinants of PH. The rate of new cardiovascular events in group with PH(59.5%) was significantly higher than that in group without PH(34%) (X2=9.203, P < 0.05). The associated variables of cardiovascular events were:systolic pulmonary arterial pressure, age, history cardiovascular disease, hs-CRP, ejection fraction, left ventricular diastolic dysfunction. In a multivariate model, the PH maintained its independent association. The mortality rate in group with PH (48.6%) was significantly higher than that in group without PH (26.4%) (X2=5.049, P < 0.05). In the Cox survival analysis, we found an association between mortality and systolic pulmonary arterial pressure, age, previous cardiovascular disease, Alb, ejection fraction. In a multivariate model the PH remains as independent predictor of mortality. Conclusion: Pulmonary hypertension is common in HD patients and a valuable predictor of mortality and cardiovascular events. [ABSTRACT FROM AUTHOR]