Dysfunctional endothelial-derived microparticles promote inflammatory macrophage formation via NF-кB and IL-1β signal pathways. Wang Yanfang,Liu Jie,Chen Xiaoli,Sun Huimin,Peng Sheng,Kuang Yashu,Pi Jingjiang,Zhuang Tao,Zhang Lin,Yu Zuoren,Tomlinson Brain,Chan Paul,Chen Yihan,Zhang Yuzhen,Li Ying Journal of cellular and molecular medicine BACKGROUND:Circulating endothelial-derived microparticles (EMPs) are reported to be increased in acute coronary syndrome (ACS). However, it remains unclear whether EMPs from dysfunctional endothelium participate in the initiation and progression of ACS and what the underlying mechanisms might be. METHODS:Plasma EMPs were measured in 22 patients with ACS and 20 control patients without coronary artery diseases. EMPs from dysfunctional human umbilical vein endothelial cells (HUVECs) stressed by serum-starvation or hypoxia were compared to the EMPs from healthy HUVECs. Confocal and fluorescent microscopy was used to visualize the incorporation of EMPs into monocytes and the translocation of NF-кB. Monocyte adhesion, cell proliferation, and phagocytosis were detected by PKH26 red fluorescent labelling, Ki67 immunostaining, and Sudan IV staining for uptake of oxidized low-density lipoprotein, respectively. RESULTS:Plasma EMPs was significantly increased in ACS patients compared to controls. EMPs were incorporated into monocytes and EMPs from stressed HUVECs produced more pro-inflammatory cytokines compared to vehicle control, which was depended on NF-кB and IL-1β signal pathways. EMPs from dysfunctional endothelium promoted monocyte adherence via NF-кB and IL-1β-mediated MCP-1 and CCR-5 signals, as well as proliferation via the NF-кB and IL-1β-mediated Cyclin D1 signals. Finally, EMPs from dysfunctional endothelium showed greater promotion of macrophage phagocytosis forming foam cells to produce more pro-inflammatory cytokines. CONCLUSION:MPs might be involved in the inflammatory process in patients with ACS via NF-κB and IL-1β-dependent signals. Targeting EMP-mediated inflammatory responses may be a promising therapeutic strategy to limit the progression of disease in ACS. 10.1111/jcmm.13950

Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial infarction. Lee Seung-Jun,Lee Choong-Kun,Kang Seok,Park Intae,Kim Yoo Hyung,Kim Seo Ki,Hong Seon Pyo,Bae Hosung,He Yulong,Kubota Yoshiaki,Koh Gou Young The Journal of clinical investigation Emerging evidence indicates that angiopoietin-2 (Angpt2), a well-recognized vascular destabilizing factor, is a biomarker of poor outcome in ischemic heart disease. However, its precise role in postischemic cardiovascular remodeling is poorly understood. Here, we show that Angpt2 plays multifaceted roles in the exacerbation of cardiac hypoxia and inflammation after myocardial ischemia. Angpt2 was highly expressed in endothelial cells at the infarct border zone after myocardial infarction (MI) or ischemia/reperfusion injury in mice. In the acute phase of MI, endothelial-derived Angpt2 antagonized Angpt1/Tie2 signaling, which was greatly involved in pericyte detachment, vascular leakage, increased adhesion molecular expression, degradation of the glycocalyx and extracellular matrix, and enhanced neutrophil infiltration and hypoxia in the infarct border area. In the chronic remodeling phase after MI, endothelial- and macrophage-derived Angpt2 continuously promoted abnormal vascular remodeling and proinflammatory macrophage polarization through integrin α5β1 signaling, worsening cardiac hypoxia and inflammation. Accordingly, inhibition of Angpt2 either by gene deletion or using an anti-Angpt2 blocking antibody substantially alleviated these pathological findings and ameliorated postischemic cardiovascular remodeling. Blockade of Angpt2 thus has potential as a therapeutic option for ischemic heart failure. 10.1172/JCI99659