Latexin deficiency limits foam cell formation and ameliorates atherosclerosis by promoting macrophage phenotype differentiation.

Autor: He G; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, China., Ni Y; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, China., Hua R; Department of Scientific Research, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China., Wan H; Heyuan Research Center for Cardiovascular Diseases, Department of Cardiology, the Fifth Affiliated Hospital of Jinan University, Heyuan, Guangdong, China., Tan Y; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, China., Chen Q; Department of Scientific Research, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China., Xu S; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, China., Yang Y; Department of Pathology, Affiliated Hospital of Guilin Medical College, Guilin, China., Zhang L; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, China., Shu W; College of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin, China., Huang KB; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, China., Mo Y; Biobank department, The reproductive hospital of Guangxi Zhuang autonomous region, Nanning, China., Liang H; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, China. hliang@gxnu.edu.cn., Chen M; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, China. chenmingprotein@mailbox.gxnu.edu.cn.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2024 Oct 18; Vol. 15 (10), pp. 754. Date of Electronic Publication: 2024 Oct 18.
DOI: 10.1038/s41419-024-07141-3
Abstrakt: Latexin (LXN) is abundant in macrophages and plays critical roles in inflammation. Much is known about macrophages in atherosclerosis, the role of macrophage LXN in atherosclerosis has remained elusive. Here, the expression of LXN in human and mouse atherosclerotic lesions was examined by immunofluorescence and immunohistochemistry. LXN knockout and LXN/ApoE double-knockout mice were generated to evaluate the functions of LXN in atherosclerosis. Bone marrow transplantation (BMT) experimentation was carried out to determine whether macrophage LXN regulates atherosclerosis. We found that LXN is enriched in human and murine atherosclerotic lesions, mainly localized to macrophages. LXN deletion ameliorated atherosclerosis in ApoE -/- mice. BMT demonstrate that deletion of LXN in bone marrow protects ApoE -/- mice against atherosclerosis. Mechanistically, we found that LXN targets and inhibits JAK1 in macrophages. LXN deficiency stimulates the JAK1/STAT3/ABC transporter pathway, thereby enhancing the anti-inflammatory and anti-oxidant phenotype, cholesterol efflux, subsequently minimizing foam cell formation and atherosclerosis. Gene therapy by treatment of atherosclerotic mice with adeno-associated virus harbouring LXN-depleting shRNA attenuated the disease phenotype. In summary, our study provides new clues for the role of LXN in the pathological regulation of atherosclerosis, and determines that LXN is a target for preventing atherosclerosis, which may be a potential new anti-atherosclerosis therapeutic target.
(© 2024. The Author(s).)
Databáze: MEDLINE
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