心力衰竭
压力过载
中性粒细胞胞外陷阱
渗透(HVAC)
恶化
炎症
医学
心室重构
免疫学
内科学
材料科学
复合材料
心肌肥大
作者
Mengmeng Zhao,Zihui Zheng,Zheng Yin,Jishou Zhang,Shanshan Peng,Jianfang Liu,Wei Pan,Cheng Wei,Yao Xu,Juan‐Juan Qin,Jun Wan,Menglong Wang
标识
DOI:10.1016/j.bcp.2023.115912
摘要
Recent studies have shown that neutrophils play an important role in the development and progression of heart failure. Developmental endothelial locus-1 (DEL-1) is an anti-inflammatory glycoprotein that has been found to have protective effects in various cardiovascular diseases. However, the role of DEL-1 in chronic heart failure is not well understood. In a mouse model of pressure overload-induced non-ischemic cardiac failure, we found that neutrophil infiltration in the heart increased and DEL-1 levels decreased in the early stages of heart failure. DEL-1 deficiency worsened pressure overload-induced cardiac dysfunction and remodeling in mice. Mechanistically, DEL-1 deficiency promotes neutrophil infiltration and the formation of neutrophil extracellular traps (NETs) through the regulation of P38 signaling. In vitro experiments showed that DEL-1 can inhibit P38 signaling and NETs formation in mouse neutrophils in a MAC-1-dependent manner. Depleting neutrophils, inhibiting NETs formation, and inhibiting P38 signaling all reduced the exacerbation of heart failure caused by DEL-1 deletion. Overall, our findings suggest that DEL-1 deficiency worsens pressure overload-induced heart failure by promoting neutrophil infiltration and NETs formation.
科研通智能强力驱动
Strongly Powered by AbleSci AI