Anti-Inflammatory Responses Produced with <i>Nippostrongylus brasiliensis</i>-Derived Uridine via the Mitochondrial ATP-Sensitive Potassium Channel and Its Anti-Atherosclerosis Effect in an Apolipoprotein E Gene Knockout Mouse Model
Yingshu Zhang,
Xin Ding,
Caiyi Yuan,
Yougui Yang,
Qiang Zhang,
Jiakai Yao,
Ying Zhang,
Junhong Wang,
Yang Dai
Affiliations
Yingshu Zhang
School of Public Health, Nanjing Medical University, Longmian Avenue 101, Nanjing 211166, China
Xin Ding
Jiangsu Provincial Medical Key Laboratory, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Institute of Parasitic Diseases, Yang Xiang 117, Wuxi 214064, China
Caiyi Yuan
School of Public Health, Nanjing Medical University, Longmian Avenue 101, Nanjing 211166, China
Yougui Yang
School of Public Health, Nanjing Medical University, Longmian Avenue 101, Nanjing 211166, China
Qiang Zhang
Jiangsu Provincial Medical Key Laboratory, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Institute of Parasitic Diseases, Yang Xiang 117, Wuxi 214064, China
Jiakai Yao
Jiangsu Provincial Medical Key Laboratory, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Institute of Parasitic Diseases, Yang Xiang 117, Wuxi 214064, China
Ying Zhang
Jiangsu Provincial Medical Key Laboratory, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Institute of Parasitic Diseases, Yang Xiang 117, Wuxi 214064, China
Junhong Wang
Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing 210029, China
Yang Dai
School of Public Health, Nanjing Medical University, Longmian Avenue 101, Nanjing 211166, China
Atherosclerosis (AS) has become the leading cause of cardiovascular disease worldwide. Our previous study had observed that Nippostrongylus brasiliensis (Nb) infection or its derived products could inhibit AS development by inducing an anti-inflammatory response. We performed a metabolic analysis to screen Nb-derived metabolites with anti-inflammation activity and evaluated the AS-prevention effect. We observed that the metabolite uridine had higher expression levels in mice infected with the Nb and ES (excretory–secretory) products and could be selected as a key metabolite. ES and uridine interventions could reduce the pro-inflammatory responses and increase the anti-inflammatory responses in vitro and in vivo. The apolipoprotein E gene knockout (ApoE−/−) mice were fed with a high-fat diet for the AS modeling. Following the in vivo intervention, ES products or uridine significantly reduced serum and liver lipid levels, alleviated the formation of atherosclerosis, and reduced the pro-inflammatory responses in serum or plaques, while the anti-inflammatory responses showed opposite trends. After blocking with 5-HD (5-hydroxydecanoate sodium) in vitro, the mRNA levels of M2 markers were significantly reduced. When blocked with 5-HD in vivo, the degree of atherosclerosis was worsened, the pro-inflammatory responses were increased compared to the uridine group, while the anti-inflammatory responses decreased accordingly. Uridine, a key metabolite from Nippostrongylus brasiliensis, showed anti-inflammatory and anti-atherosclerotic effects in vitro and in vivo, which depend on the activation of the mitochondrial ATP-sensitive potassium channel.
