Hyperuricemia is an important risk factor for vascular inflammation, yet the potential mechanisms of uric acid (UA) in endothelial cells are not well understood. UA has been found to stimulate renin-angiotensin system (RAS) activation in human umbilical vein endothelial cells (HUVECs). (Pro)renin receptor ((P)RR) is widely expressed in endothelial cells and able to induce RAS activation. Whether UA-induced endothelial cell inflammation is via up-regulating (P)RR remained unknown. Primary HUVECs were cultured and treated with UA, under the condition of (P)RR or AT1 silencing. The degree of inflammation in HUVECs was determined by Real-time PCR and monocyte adhesion assay. The protein levels of (P)RR were determined by western blotting or immunofluorescence. Probenecid was used to block UA re-absorption in this study. Adhesion of monocytes to HUVECs was elucidated by microfluidic chip. We found (P)RR is up-regulated in HUVECs following UA stimulation. UA promoted vascular inflammation, which was characterized by up-regulating of cytokines and enhanced monocyte adhesion. Silencing of (P)RR alleviated UA-induced vascular inflammation. Probenecid treatment abolished UA-induced vascular inflammation in HUVECs via suppressing (P)RR up-regulation. This finding was further verified by using microfluidic chip. Our findings indicate that (P)RR plays a critical role in endothelial inflammation in response to UA stimulation.

This study aimed to explore whether brachial‐ankle pulse wave velocity (baPWV) and brachial artery flow‐mediated dilation (FMD) or the interaction of both parameters are associated with subclinical target organ damage (STOD) indices in patients with essential hypertension. A total of 4618 patients registered from January 2015 to October 2020 were included. baPWV and FMD were measured to evaluate arterial stiffness and endothelial dysfunction. Whereas left ventricular hypertrophy (LVH), urine albumin‐creatinine ratio (UACR), and carotid intima‐media thickness (CIMT) were obtained as STOD indicators. On multivariable logistic regression analysis with potential confounders, higher quartiles of baPWV and FMD were significantly associated with an increased risk of STOD. In patients <65 years of age, the odds ratio (OR) of LVH, UACR, and CIMT ≥.9 mm for the fourth versus the first quartile of baPWV were 1.765 (1.390–2.240), 2.832 (2.014–3.813), and 3.075 (2.315–4.084), respectively. In interaction analysis, an increase in baPWV shows a progressively higher risk of STOD across the quartiles of FMD. Also, the estimated absolute risks of LVH, UACR, and CIMT ≥.9 mm for the first to fourth quartile of baPWV increased from 1.88 to 2.75, 2.35 to 4.44, and 3.10 to 6.10, respectively, in patients grouped by FMD quartiles. The addition of baPWV to FMD slightly improved risk prediction for STOD. BaPWV and FMD were independently associated with an increased risk of STOD in patients with essential hypertension especially among patients <65 years of age. Patients with elevated baPWV and decreased FMD parameters are at increased risk of STOD.

Background/Aims: Angiotensin II (Ang II) mediated signaling plays a key role in the development of chronic kidney damage that contributes to renal fibrosis. However, the gene expression changes regulated by Ang II in the early stage of acute renal injury remain unclear. Methods: C57BL/6 wild-type (WT) mice were injected with Ang II (1500 ng/kg/min) for 1, 3 and 7 days. A time series analysis of microarrays was performed to evaluate Ang II-induced differentially gene expression in the kidneys. The data of gene expression in the kidney was further dissected by ANOVA analysis, gene expression profiles, gene network construction and quantitative real-time RT-PCR. Ang II-induced renal inflammation and fibrosis in mice were confirmed by pathological examination. Results: Our microarray data showed that a total of 1,511 differentially expressed genes were identified in the kidneys at 1, 3 and 7 days after Ang II infusion. These genes function in multiple biological processes, including response to stimuli, immune response, cell adhesion, metabolic process, kidney development, regulation of blood pressure, and ion transport, which may play critical roles in the pathobiology of Ang II-induced acute renal injury at the early stage. Furthermore, among these genes, 20 genes were further selected for final investigation. The dynamic gene network analysis demonstrated that fatty acid binding protein 1 (Fabp1) localized in the core of the network. Conclusions: Our data suggests that genes involved in lipid metabolic process, especially Fabp1, may play a central role in the development of Ang II-induced acute renal injury at the early stage.

Objectives. Aldosterone-to-plasma renin activity ratio (ARR) derived from traditional radioimmunoassay (RIA) is widely used to detect primary aldosteronism (PA). Recently, aldosterone-to-direct renin concentration ratio (ADRR), which is calculated by direct renin concentration (DRC) measured by chemiluminescent immunoassay (CLIA), is proposed to replace ARR as the screening test method for PA. The purpose of the present study was to estimate the diagnostic accuracy and cutoff value of ADRR as screening test for PA. Methods. 450 hypertensive patients with suspected PA referred to hypertension center of our department were enrolled and underwent screening and confirmatory tests of PA. Plasma renin activity (PRA), DRC, and plasma aldosterone concentration (PAC) were measured by both RIA and CLIA simultaneously during screening and confirmatory test. Results. 386 patients were diagnosed as primary hypertension (PH) and 64 patients as PA. Within-patient correlation between PRA and DRC (r=0.88, P<0.001) and correlation between PAC measured by RIA and CLIA were high (r=0.80, P<0.001). The optimal cutoff value of ADRR was 2.93 (ng/dL)/(mU/L), sensitivity 80.33%, and specificity 92.11%. The optimal cutoff value of ARR was 25.28 (ng/dL)/(ng/mL/h), sensitivity 76.92%, and specificity 93.38%. Conclusion. The optimal cutoff values of ADRR and ARR for screening PA are defined in this patient cohort with high sensitivity and specificity. Our results are of clinical importance for accelerating the extensive use of ADRR as a screening test for PA in daily practice.