Article: Genetic ablation of myeloid integrin α9 attenuates early atherosclerosis

Authors: Tarun Barbhuyan, Rakesh B Patel, Ivan Budnik, Anil K Chauhan

Journal: J Leukoc Biol. 2024 Jul 22:qiae161. doi: 10.1093/jleuko/qiae161.

Abstract:
Integrin α9β1 is known to stabilize leukocyte adhesion to the activated endothelium. We determined the role of myeloid cell α9β1 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 BM→Ldlr-/- mice (p<0.05 vs α9WT BM→Ldlr-/- 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.

Link to journal online: https://academic.oup.com/jleukbio/advance-article/doi/10.1093/jleuko/qiae161/7717840