BACKGROUND The inflammatory response caused by the NLRP3 is closely related to the formation of myocardial ischemiareperfusion injury.Costimulatory receptor CD137 and its ligand play a crucial role in regulating the i...BACKGROUND The inflammatory response caused by the NLRP3 is closely related to the formation of myocardial ischemiareperfusion injury.Costimulatory receptor CD137 and its ligand play a crucial role in regulating the inflammatory immune response in atherosclerosis,which is the fundamental cause of cardiovascular diseases.However,the roles of CD137 signaling in the process of myocardial ischaemia-reperfusion(IR)injury remain unknown.METHODS Genetic ablation was used to determine the functional significance of CD137 in myocardial IR injury.Expression of CD137 was examined by Western-blot,quantitative real-time polymerase chain reaction,and immunohistochemistry in a murine IR model by coronary artery ligation.Even’s blue-TTC staining and echocardiography to evaluate the severity of myocardial IR injury.Furthermore,HL-1 cardiomyocytes treated with agonist-CD137 recombinant protein were used to explore the underlying mechanism in CD137 signaling-induced NLRP3 inflammasome activation in response to hypoxia/reoxygenation or LPS/ATP.RESULTS We demonstrated that CD137 knockout significantly improved cardiac function,accompanied by a markedly reduced NLRP3-mediated inflammatory response and IA/AAR which were reversed by mitophagy inhibitor Mdivi-1.Activating CD137 signaling significantly inhibited mitophagy and provoked NLRP3-mediated inflammatory response in H/R-injured or LPS-primed and ATP-stimulated HL-1 cardiomyocytes,the effects of which could be abolished by either anti-CD137 or mitophagy activator FCCP.Besides,mitochondrial ROS was augmented by activating CD137 signaling through the suppression of mitophagy.CONCLUSIONS Our results reveal that activating CD137 signaling aggravates myocardial IR injury by upregulating NLRP3 inflammasome activation via suppressing mitophagy and promoting mtROS generation.展开更多
Diabetes mellitus is a kind of typical metabolic disorder characterized by elevated blood sugar levels.Atherosclerosis(AS)is one of the most common complications of diabetes.Modern lifestyles and trends that promote o...Diabetes mellitus is a kind of typical metabolic disorder characterized by elevated blood sugar levels.Atherosclerosis(AS)is one of the most common complications of diabetes.Modern lifestyles and trends that promote overconsumption and unhealthy practices have contributed to an increase in the annual incidence of diabetic AS worldwide,which has created a heavy burden on society.Several studies have shown the significant effects of glycolysis-related changes on the occurrence and development of diabetic AS,which may serve as novel therapeutic targets for diabetic AS in the future.Glycolysis is an important metabolic pathway that generates energy in various cells of the blood vessel wall.In particular,it plays a vital role in the physiological and pathological activities of the three important cells,Endothelial cells,macrophages and vascular smooth muscle cells.There are lots of similar mechanisms underlying diabetic and common AS,the former is more complex.In this article,we describe the role and mechanism underlying glycolysis in diabetic AS,as well as the therapeutic targets,such as trained immunity,microRNAs,gut microbiota,and associated drugs,with the aim to provide some new perspectives and potentially feasible programs for the treatment of diabetic AS in the foreseeable future.展开更多
基金supported as follows:National Natural Science Foundation of China(81970379)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22_3712)Medical Innovation Team Project of Jiangsu Province(CXTDA2017010).
文摘BACKGROUND The inflammatory response caused by the NLRP3 is closely related to the formation of myocardial ischemiareperfusion injury.Costimulatory receptor CD137 and its ligand play a crucial role in regulating the inflammatory immune response in atherosclerosis,which is the fundamental cause of cardiovascular diseases.However,the roles of CD137 signaling in the process of myocardial ischaemia-reperfusion(IR)injury remain unknown.METHODS Genetic ablation was used to determine the functional significance of CD137 in myocardial IR injury.Expression of CD137 was examined by Western-blot,quantitative real-time polymerase chain reaction,and immunohistochemistry in a murine IR model by coronary artery ligation.Even’s blue-TTC staining and echocardiography to evaluate the severity of myocardial IR injury.Furthermore,HL-1 cardiomyocytes treated with agonist-CD137 recombinant protein were used to explore the underlying mechanism in CD137 signaling-induced NLRP3 inflammasome activation in response to hypoxia/reoxygenation or LPS/ATP.RESULTS We demonstrated that CD137 knockout significantly improved cardiac function,accompanied by a markedly reduced NLRP3-mediated inflammatory response and IA/AAR which were reversed by mitophagy inhibitor Mdivi-1.Activating CD137 signaling significantly inhibited mitophagy and provoked NLRP3-mediated inflammatory response in H/R-injured or LPS-primed and ATP-stimulated HL-1 cardiomyocytes,the effects of which could be abolished by either anti-CD137 or mitophagy activator FCCP.Besides,mitochondrial ROS was augmented by activating CD137 signaling through the suppression of mitophagy.CONCLUSIONS Our results reveal that activating CD137 signaling aggravates myocardial IR injury by upregulating NLRP3 inflammasome activation via suppressing mitophagy and promoting mtROS generation.
文摘目的探讨糖尿病患者诊断应用血清C肽联合糖化血红蛋白检测的价值。方法将2022年1月—2023年1月泗阳康达医院收治的74例疑似糖尿病患者作为研究对象,检测入组患者糖化血红蛋白(glycosylated hemoglobin,HbA1c)以及血清C肽水平,以口服葡萄糖耐量试验(glucose tolerance test check,OGTT)为金标准,统计血清C肽联合糖化血红蛋白检测与单一项目检测的敏感性、特异度和诊断符合率。结果74例疑似糖尿病患者根据葡萄糖耐量试验结果,确诊患者67例,确诊率为90.54%(67/74);与血清C肽、HbA1c单一检测相比,血清C肽+HbA1c联合检测敏感度更高,差异有统计学意义(P<0.05);血清C肽+HbA1c联合检测的特异度略高于血清C肽、HbA1c单一检测,但差异无统计学意义(P>0.05);联合检测诊断符合率明显高于血清C肽、HbA1c单项检测,差异有统计学意义(P<0.05)。结论血清C肽与糖化血红蛋白是临床诊断糖尿病的重要参考指标,二者表达水平的变化有助于检测患者胰岛素分泌功能,评估疾病严重程度,两者联合检验灵敏性与特异度良好,有助于早期明确诊断,临床参考价值较高。
基金the Cardiovascular Disease Clinical Research Center of Zhenjiang,No.SS2018008Social Development Foundation of Jiangsu,No.BE2021694and Jiangsu Provincial 333 Talent Project,No.BRA2020.
文摘Diabetes mellitus is a kind of typical metabolic disorder characterized by elevated blood sugar levels.Atherosclerosis(AS)is one of the most common complications of diabetes.Modern lifestyles and trends that promote overconsumption and unhealthy practices have contributed to an increase in the annual incidence of diabetic AS worldwide,which has created a heavy burden on society.Several studies have shown the significant effects of glycolysis-related changes on the occurrence and development of diabetic AS,which may serve as novel therapeutic targets for diabetic AS in the future.Glycolysis is an important metabolic pathway that generates energy in various cells of the blood vessel wall.In particular,it plays a vital role in the physiological and pathological activities of the three important cells,Endothelial cells,macrophages and vascular smooth muscle cells.There are lots of similar mechanisms underlying diabetic and common AS,the former is more complex.In this article,we describe the role and mechanism underlying glycolysis in diabetic AS,as well as the therapeutic targets,such as trained immunity,microRNAs,gut microbiota,and associated drugs,with the aim to provide some new perspectives and potentially feasible programs for the treatment of diabetic AS in the foreseeable future.
