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The underlying targets and mechanisms of sepsis-induced myocardial dysfunction (SIMD) in sepsis are awaiting profound exploration. The present study investigates the contribution and mechanism of asialoglycoprotein receptor 1 (ASGR1)1 to the progression of SIMD. Herein, we show that ASGR1 in heart tissue is highly related to SIMD. Anti-Ly6G and GSK484 deplete neutrophils and neutrophil extracellular traps (NETs), alleviating myocardial injury and cardiac dysfunction and promoting survival of LPS-challenged mice. Neutrophils and NETs are observably declined in ASGR1 knockout mice and conditional knockout neutrophils, respectively. In ASGR1 deficiency mice, LPS challenge results in elevated neutrophils and NETs using flow cytometric analysis and confocal microscopy, respectively, leading to reduced myocardial dysfunction and mortality. ASGR1 promotes neutrophil activation and NET accumulation via SLC7A11-dependent ferroptosis. ASGR1 acts as a bridge to transfer the attached ubiquitin to SLC7A11 and facilitates K48-linked ubiquitination degradation of SLC7A11 by SOCS2. Our findings suggest that ASGR1 is a principal indicator of SIMD by inducing NET formation. In addition, the regulation of NET formation could be a potential treatment for SIMD.<\/jats:p>","DOI":"10.1042\/cs20250290","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T14:55:39Z","timestamp":1776783339000},"page":"1199-1221","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ASGR1 induces neutrophil extracellular traps formation to exacerbate sepsis-induced myocardial injury and cardiac dysfunction through SLC7A11 ubiquitination"],"prefix":"10.1042","volume":"140","author":[{"given":"Rui","family":"Shi","sequence":"first","affiliation":[{"name":"1Department of Pharmacy, The First Affiliated Hospital of Kunming Medical University, Kunming, China"},{"name":"2School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"3Department of Emergency, The First Affiliated Hospital of Kunming Medical University, Kunming, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaozhong","family":"Li","sequence":"additional","affiliation":[{"name":"3Department of Emergency, The First Affiliated Hospital of Kunming Medical University, Kunming, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang","family":"Xiao","sequence":"additional","affiliation":[{"name":"2School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyun","family":"Bai","sequence":"additional","affiliation":[{"name":"4Yunnan Institute for Food and Drug Control, Kunming, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9792-0916","authenticated-orcid":false,"given":"Alex\u00a0F","family":"Chen","sequence":"additional","affiliation":[{"name":"5Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7505-7122","authenticated-orcid":false,"given":"Weimin","family":"Yang","sequence":"additional","affiliation":[{"name":"2School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"2026061006212019300_B1","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1159\/000064283","article-title":"Expression of a functional asialoglycoprotein receptor in human renal proximal tubular epithelial cells","volume":"91","author":"Seow","year":"2002","journal-title":"Nephron"},{"key":"2026061006212019300_B2","doi-asserted-by":"publisher","first-page":"20218","DOI":"10.1073\/pnas.1313905110","article-title":"Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor","volume":"110","author":"Grewal","year":"2013","journal-title":"Proc. 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