CD137 signaling aggravates myocardial ischemia-reperfusion injury by inhibiting mitophagy mediated NLRP3 inflammasome activation

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.

Advances in neovascularization after diabetic ischemia

With the high incidence of diabetes around the world,ischemic complications cause a serious influence on people’s production and living.Neovascularization plays a significant role in its development.Therefore,neovascularization after diabetic ischemia has aroused attention and has become a hot spot in recent years.Neovascularization is divided into angiogenesis represented by atherosclerosis and arteriogenesis characterized by coronary collateral circulation.When mononuclear macrophages successively migrate to the ischemia anoxic zone after ischemia or hypoxia,they induce the secretion of cytokines,such as vascular endothelial growth factor and hypoxia-inducible factor,activate signaling pathways such as classic Wnt and phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)pathways,trigger oxidative stress response,activate endothelial progenitor cells or enter the glycolysis or lactic acid process and promote the formation of new blood vessels,remodeling them into mature blood vessels and restoring blood supply.However,the hypoglycemic condition has different impacts on neovascularization.Consequently,this review aimed to introduce the mechanisms of neovascularization after diabetic ischemia,increase our understanding of diabetic ischemic complications and their therapies and provide more treatment options for clinical practice and effectively relieve patients’pain.It is believed that in the near future,neovascularization will bring more benefits and hope to patients with diabetes.

The primary use of artificial intelligence in cardiovascular diseases: what kind of potential role does artificial intelligence play in future medicine?

Cardiovascular diseases (CVD) is a major threat to human health and the leading cause of death worldwide.[1] The incidence of CVD caused 17.6 million deaths in 2016, an increase of 14.5% from 2006 to 2016.[2] Unfortunately, the mortality and morbidity rates of CVD are increasing year by year, especially in developing regions. Studies have shown that approximately 80% of CVD-related deaths occur in low- and middle-income countries. Besides, these deaths occur at a younger age than in high-income countries.[3]?