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Hypertension is one of the leading causes of chronic kidney disease characterized with renal fibrosis. This study aimed to investigate roles and mechanisms of sirtuin 7 (SIRT7) in hypertensive renal injury. Mini-pumps were implanted to male C57BL/6 mice to deliver angiotensin (Ang) Ⅱ (1.5 mg/kg/d) or saline for 2 weeks. Ang Ⅱ infusion resulted in marked increases in systolic blood pressure levels, renal ferroptosis and interstitial fibrosis in hypertensive mice, concomitantly with downregulated SIRT7 and Krüppel-like factor 15 (KLF15) levels. Notably, administration of recombinant adeno-associated virus-SIRT7 or ferroptosis inhibitor ferrostatin-1 effectively mitigated Ang Ⅱ-triggered renal ferroptosis, epithelial-mesenchymal transition (EMT), interstitial fibrosis, renal functional and structural injury in hypertensive mice by blunting the KIM-1/NOX4 signaling and enforcing the KLF15/Nrf2 and xCT/GPX4 signaling, respectively. In primary cultured mouse renal tubular epithelial cells (TECs), Ang Ⅱ pretreatment led to repressed SIRT7 expression and augmented ferroptosis as well as partial EMT, which were substantially antagonized by rhSIRT7 or ferrostatin-1 administration. Additionally, both Nrf2 inhibitor ML385 and KLF15 siRNA strikingly abolished the rhSIRT7-mediated beneficial roles in mouse renal TECs in response to Ang Ⅱ with reduced expression of Nrf2, xCT and GPX4. More importantly, ML385 administration remarkably amplified Ang Ⅱ-mediated ROS generation, lipid peroxidation and ferroptosis in renal TECs, which were significantly reversed by ferrostatin-1. In conclusion, SIRT7 alleviates renal ferroptosis, lipid peroxidation, and partial EMT under hypertensive status by facilitating the KLF15/Nrf2 signaling, thereby mitigating renal fibrosis, injury and dysfunction. Targeting SIRT7 signaling serves as a promising strategy for hypertension and hypertensive renal injury.

Aim The purpose of this study was to assess the outcome of out-of-hospital cardiac arrests (OHCAs) in Beijing, China. Methods In this prospective study, data were collected according to the Utstein style on all cases of OHCA that occurred between January and December 2012 in urban areas covered by Beijing Emergency Medical Services (EMS). The cases were followed-up for 1 year. Results Out of the 9897 OHCAs recorded, cardiopulmonary resuscitation (CPR) was initiated in 2421 patients (24.4%). Among the CPR-receivers ( n =2421), 1804 patients (74.5%) had collapsed at home, while 375 patients (15.5%) at a public place. The average time interval from call to EMS arrival at the collapse location was 16min (range, 4–43min). Of the 1693 OHCA cases with cardiac aetiology, 1246 cases (73.6%) were witnessed, and basic CPR was performed by bystanders before arrival of the EMS personnel in 193 patients (11.4%). Of the OHCAs with cardiac aetiology, 1054 patients (62.3%) had asystole, 131 patients (7.7%) had shockable rhythms, restoration of spontaneous circulation was achieved in 85 patients (5.0%), 71 patients (4.2%) were admitted to the hospital alive, and of the 22 patients (1.3%) who were discharged alive, 17 patients (1%) had good neurological outcomes. At 1 year post-OHCA, 17 patients were alive. Conclusion In the urban areas of Beijing with EMS services, survival rate after OHCA was unsatisfactory. Improvements are required in every link of the ‘chain of survival'.