Genetic ablation of myeloid integrin α9 attenuates early atherosclerosis.
J Leukoc Biol
; 2024 Jul 22.
Article
em En
| MEDLINE
| ID: mdl-39036986
ABSTRACT
Integrin α9ß1 is known to stabilize leukocyte adhesion to the activated endothelium. We determined the role of myeloid cell α9ß1 in early atherosclerosis in two models α9MyeKOApoe-/- or the Ldlr-/- mice transplanted with bone marrow (BM) from α9Mye-KO mice fed a high-fat "Western" diet for four weeks. α9Mye-KOApoe-/- mice exhibited reduced early lesions in the aortae and aortic sinuses (p<0.05 vs. α9WT Apoe-/- mice). Similar results were obtained in α9Mye-KO BMâLdlr-/- mice (p<0.05 vs α9WT BMâLdlr-/- mice). Reduced early atherosclerosis in α9Mye-KOApoe-/- mice was associated with decreased neutrophil and neutrophil extracellular traps (NETs) content in the aortic lesions (p<0.05 vs. α9WTApoe-/-). VCAM-1-stimulated neutrophils from α9Mye-KO mice exhibited reduced adhesion, transmigration, and NETs formation (NETosis) (p<0.05 vs. α9WT neutrophils). Reduced NETosis was associated with decreased ERK phosphorylation, PAD4, and H3Cit expression. In summary, genetic ablation of myeloid cell-specific α9 reduces early atherosclerosis, most likely by reducing neutrophil adhesion, transmigration, and NETosis.
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MEDLINE
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Ano de publicação:
2024
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Article