Table 1.
Post-MI effect of perturbing inflammation components
| Perturbation | Effect | Mechanism |
|---|---|---|
| Reducing inflammation: | ↑LV physiology | IL-1α null: ↓innate immune response in cardiac fibroblasts |
| IL-1α null (79)TREM1 null (2)NF-κB null (60)TLR4 null (97)TRPV2 null (21)PS-presenting liposomes (39) | ↓LV remodeling | TREM1 null: ↓myeloid cell recruitment from the spleen and bone marrow; ↓CCR2+ proinflammatory but not proreparative CX3CR1+ monocyte infiltrationTLR4 null: ↓neutrophil infiltration/activationTRPV2 null: ↓macrophage migrationPS-liposomes: ↑macrophage secretion of IL-10 and TGF-β |
| Total neutrophil depletion (43, 44, 85, 86) | ↓LV physiology | ↓Necrotic myocyte removal |
| ↑Fibrosis | ↑Macrophage inflammatory response | |
| ↑Myofibroblast activation | ||
| Total macrophage depletion (120) | ↓LV physiology | Total: ↓necrotic/apoptotic cell removal |
| ↓Collagen deposition | ↓Fibroblast and endothelial cell activation | |
| M2-specific depletion (66) | ↓Neovascularization | M2: prolonged N1 neutrophil/M1 macrophage activation |
| Macrophage modulation: | ↑LV physiology | Wntless: ↑reparative M2 macrophages, neovascularization |
| Wntless null (98)Macrophage EP3R null (114)Macrophage EP3R transgenic (114)CD5L null (96) | ↓LV remodeling | EP3R null: monocyte TGF-β signaling/↓CX3CR1 and VEGF signaling, ↓Ly6Clow reparative monocyte activationEP3R transgenic: ↑angiogenesisCD5L null: ↓neutrophils, ↓collagen accumulation, ↓IL-1 receptor-associated kinase 4, NF-κB, myeloperoxidase, and inducible nitric oxide synthase |
Reference numbers are listed in parentheses. MI, myocardial infarction; TLR, Toll-like receptor; TREM1, triggering receptor expressed on myeloid cells 1; PS, phosphatidylserine; LV, left ventricular; CCR, chemokine (C-C motif) receptor; CX3CR, chemokine (C-X3-C motif) receptor; TGF-β, transforming growth factor-β; EP3R, E-prostanoid 3 receptor; ↑, increase; ↓, decrease.