| First Author | Kain V | Year | 2024 |
| Journal | J Leukoc Biol | Volume | 116 |
| Issue | 4 | Pages | 864-875 |
| PubMed ID | 38785336 | Mgi Jnum | J:359889 |
| Mgi Id | MGI:7734835 | Doi | 10.1093/jleuko/qiae113 |
| Citation | Kain V, et al. (2024) Macrophage-specific lipoxygenase deletion amplify cardiac repair activating Treg cells in chronic heart failure. J Leukoc Biol 116(4):864-875 |
| abstractText | Splenic leukocytes, particularly macrophage-expressed lipoxygenases, facilitate the biosynthesis of resolution mediators essential for cardiac repair. Next, we asked whether deletion of 12/15 lipoxygenase (12/15LOX) in macrophages impedes the resolution of inflammation following myocardial infarction (MI). Using 12/15flox/flox and LysMcre scheme, we generated macrophage-specific 12/15LOX (M-12/15LOX-/-) mice. Young C57BL/6J wild-type and M-12/15LOX-/- male mice were subjected to permanent coronary ligation microsurgery. Mice were monitored at day 1 (d1) to d5 (as acute heart failure [AHF]) and to d56 (chronic HF) post-MI, maintaining no MI as d0 naive control animals. Post ligation, M-12/15LOX-/- mice showed increased survival (88% vs 56%) and limited heart dysfunction compared with wild-type. In AHF, M-12/15LOX-/- mice have increased biosynthesis of epoxyeicosatrienoic acid by 30%, with the decrease in D-series resolvins, protectin, and maresin by 70% in the infarcted heart. Overall, myeloid cell profiling from the heart and spleen indicated that M-12/15LOX-/- mice showed higher immune cells with reparative Ly6Clow macrophages during AHF. In addition, the detailed immune profiling revealed reparative macrophage phenotype (Ly6Clow) in M-12/15LOX-/- mice in a splenocardiac manner post-MI. M-12/15LOX-/- mice showed an increase in myeloid population that coordinated increase of T regulatory cells (CD4+/Foxp3+) in the spleen and injured heart at chronic HF compared with wild-type. Thus, macrophage-specific deletion of 12/15LOX directs reparative macrophage phenotype to facilitate cardiac repair. The presented study outlines the complex role of 12/15LOX in macrophage plasticity and T regulatory cell signaling that indicates that resolution mediators are viable targets to facilitate cardiac repair in HF post-MI. |
