Table 1.
The effects of manipulating pro-resolving mediator pathways in animal models of atherosclerosis.
| Animal Model | Diet | Outcome | References | |
|---|---|---|---|---|
| Lipoxygenases | ||||
| 5-LOX knockout | Alox5−/−/Ldlr−/− | Western | ↓ aortic plaque size | 146 |
| 12/15 LOX overexpression | 12/15-LOX-transgenic Apoe−/− mice | Chow | ↓ aortic plaque size ↑ LXA4 |
147, 148 |
| 12/15 LOX overexpression | 12/15-LOX transgenic Apoe−/− mice | Western | ↔ aortic plaque size | 148 |
| 15-LOX Mφ overexpression | Human 15-LOX transgenic rabbit | Western | ↓ aortic plaque size | 149 |
| SPMs | ||||
| AT-LXA4 (osmotic pump) | Apoe−/− mice | Western | ↓ aortic plaque size | 29 |
| RvD1 (i.p.) | Ldlr−/− mice | Western | ↓ aortic plaque necrosis, ROS ↑ fibrous cap thickness, efferocytosis |
20 |
| RvD2 and MaR1 (i.p.) | Apoe−/− mice | Western | ↓ aortic plaque necrosis, Mϕ content ↑ fibrous cap thickness |
21 |
| RvE1 (p.o. gavage) | ApoE*3 Leiden transgenic mice | Western | ↓ aortic plaque size, expression of pro-atherogenic genes | 150 |
| RvE1 (p.o. topical) | Rabbit | Western | ↓ aortic plaque size, inflammatory cell infiltration | 151 |
| Receptors | ||||
| ALX/FPR2 knockout | Fpr2−/− Apoe−/− mice | Chow | ↓ aortic plaque size (16 weeks diet) | 29 |
| Western | ↔ aortic plaque size (4 weeks diet) | 29 | ||
| Fpr2−/− Ldlr−/− mice | Western | ↓ aortic plaque size (12 weeks diet) | 27 | |
| ↓Mϕ content, collagen content | ||||
| Western | ↔ aortic plaque size (16-20 weeks diet) | 27 | ||
| Fpr2−/− marrow into Ldlr−/− mice | Western | ↓ aortic plaque size (17-20 weeks diet) | 27, 30 | |
| BLT1 knockout | Blt1−/− Apoe−/− mice | Western | ↓ aortic plaque size (4-12 weeks diet) | 32, 33 |
| ↔ aortic plaque size (19 weeks diet) | 32 | |||
| ChemR23 knockout | Chemr23−/− Apoe−/− mice | Western | ↑ aortic arch plaque area, ↑ aortic root plaque size, ↑ Mϕ content (8 weeks diet) | 34 |
| Western | ↑ aortic arch plaque area, ↔ aortic root plaque size, ↑ Mϕ content (12 weeks diet) | 34 | ||
| Chemr23GFP/GFP Apoe−/− mice | Western | ↓ aortic root plaque size, ↓ Mϕ content (4 and 12 weeks diet) | 35 | |
| Chemr23−/− marrow into Ldlr−/− mice | Western | ↑ aortic plaque size, plaque necrosis, Mϕ content (12 weeks diet) | 34 | |
| Chemr23GFP/GFP marrow into Apoe−/− mice | Western | ↓ aortic plaque size (6 weeks diet) | 35 | |
| GPR32 overexpression | hGPR32mycTg Fpr2−/− Apoe−/− | ↓ aortic plaque size, plaque necrosis | 36 | |
| Pro-resolving Proteins | ||||
| Annexin A1 knockout | Anxa1−/− Apoe−/− mice | Western | ↑ aortic plaque size | 46 |
| Ac2-26 (i.v.) | Apoe−/− mice | Western | ↓ aortic plaque size and Mϕ content | 46 |
| Ac2-26 (nanoparticles i.v.) | Ldlr−/− mice | Western | ↓ aortic plaque size, plaque necrosis, ROS ↑ fibrous cap thickness |
30 |
| IL-10 knockout | Il10−/− Apoe−/− mice | Western | ↑ aortic plaque size | 41 |
| IL-10 overexpression in Mϕs | Ldlr−/− mice | Western | ↓ aortic plaque size | 42, 43 |
| IL-10 (nanoparticles i.v.) | Ldlr−− mice | Western | ↓ aortic plaque necrosis, ROS | 44 |
| ↑ fibrous cap thickness | ||||
Modified from Kasikara, Doran, et al.15