Table 2. In vivo effects of apoprotein mimetic peptides.
| Name | Lipid and Lipoprotein Effects | Atherosclerosis and Vascular Effects | Reference |
|---|---|---|---|
| Monomeric ApoA-I Mimetic Peptides | |||
| 2F (Ac-18-NH2) | elutes with HDL | No effect | 34, 77 |
| 3F-2 | associates with HDL | ↓ aortic root lesion in 10 wk old apoE-/- mice (6 wk treatment) | 18 |
| 3F-14 | associates with apoB containing lipoproteins | No effect on aortic root lesions in 10 wk old apoE-/- mice (6 wk treatment) | 18 |
| 4F | ↓ plasma cholesterol (oral delivery, not IP) | No effect on aortic root lesion in 20 wk old apoE-/- mice fed HFD (4 wk treatment) | 63 |
| No effect | ↓ aortic root in LDLR-/- mice (6 wk treatment in liposomes) | 62 | |
| No effect | ↓ aortic root in 9 wk old apoE-/- mice (4 wk treatment in water) | 62 | |
| ↓ plasma cholesterol ↑ plasma triglyceride ↓ SAA |
↓ en face aortic lesions in HDF fed rabbits (4 wk treatment SC) | 78 | |
| ↑ HDL cholesterol and PON activity | ↓ lesions in 21 wk old apoE-/- mice treated with statin (17 wk treatment) ↓ lesions in 1 yr old apoE-/- mice treated with statin (6 month treatment) |
64 | |
| ↓ aortic root and en face aortic lesions in 15.5 month old apoE-/- mice treated with statin (6 month treatment) | 25 | ||
| elutes with HDL and preβ-HDL (LDLR-/-mice) ↑ PON activity (monkey) ↓ LOOH in human HDL |
34 | ||
| ↑ reverse cholesterol transport ↓ LOOH in VLDL/LDL/HDL (<24 hr treatment) ↑ LOOH in preβ-HDL |
31 | ||
| does not elute with HDL no effect on PON no effect on plasma lipids ↑ antibodies to oxidized phospholipids |
No effect on lesions in 28 wk old apoE-/- mice (8 wk treatment IP) ↓ aortic arch and innominate artery lesions in 14 wk old apoE-/- mice (4 week treatment IP) |
35, Wool et al. unpublished | |
| No effect | ↑ vasodilation in LDLR-/- on HFD (2-6 wk treatment) | 66, 67 | |
| 5F | binds HDL⋙VLDL decreases HDL in cholate diet fed mice |
↓ aortic lesion in wild type mice on cholate diet (16 wk treatment) | 65 |
| Tandem apoA-I Mimetic Peptides | |||
| 37pA (18A-Pro-18A) | elutes with HDL | 77 | |
| 5A (18A-Pro-18A with Ala substitutions in 2nd helix) | ↓ adhesion molecule expression with 5A/PL complexes (rabbits) | 68 | |
| 4F-Ala-4F | no effect with 1 wk treatment | 35 | |
| 4F-Pro-4F | ↑ IDL/LDL levels no effect on PON ↓ SAA (short term treatment) ↑ antibodies to oxidized phospholipids |
no effect on lesions in 14 wk old apoE-/- mice (4 week treatment) or 28 wk old apoE-/- mice (8 wk treatment) | 35, Wool et al unpublished |
| Peptides mimicking other apoproteins | |||
| [113-122]apoJ | elutes in late HDL ↑ HDL ↓ total cholesterol ↑ PON |
↓ aortic lesions in 30 wk old apoE-/- mice (24 wk treatment) | 45 |
| apoE AcY(141-155)2 | -rapid ↓ VLDL/IDL | 48 | |
| Ac-hE-18A-NH2 [(141-150)-18A] | ↓ VLDL and LDL in mice and WHHL rabbits ↑ PON (WHHL rabbits) ↓ LOOH plasma levels (WHHL rabbits) |
improves vasorelaxation (WHHL rabbits) | 50, 51, 78 |
| ATI-5261 | no effect | ↓ aortic lesions in LDLR-/- mice fed HFD for 13 weeks (6 wk treatment) ↓ aortic and aortic sinus lesions in apoE-/-mice fed HFD 18 wks (switched to chow diet and treated for 6 wks) |
53 |
| mSAA2.1(1-20) | no effect | ↓ aortic lesions in 14 wk old apoE-/- mice fed HFD with cholate (2 wk treatment) | 57 |
| mSAA2.1(74-103) | no effect | ↓ aortic lesions in 14 wk old apoE-/- mice fed HFD with cholate (2 wk treatment) additional therapeutic effect when co-administered with mSAA2.1 (1-20) |
57 |
| Generically amphipathic Peptides | |||
| KRES | elutes with HDL ↑ HDL ↑ PON activity ↓ LOOH in LDL and HDL |
- ↓ aortic lesions in 18 wk old apoE-/- mice (12 wk treatment) | 58 |
| KERS | does not bind HDL no effect on HDL levels no effect on PON |
- no effect | 58 |
| FREL | elutes with HDL ↑ HDL ↑ PON activity ↓ LOOH in LDL and HDL |
- ↓ aortic lesions in 18 wk old apoE-/- mice (12 wk treatment) | 58 |