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
Biochemical pharmacology 2023 DecRecent 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. Copyright © 2023. Published by Elsevier Inc.
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. DEL-1 deficiency aggravates pressure overload-induced heart failure by promoting neutrophil infiltration and neutrophil extracellular traps formation. Biochemical pharmacology. 2023 Dec;218:115912
PMID: 37956894
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