Table 1.
Selected HDL and apoA-I regression studies
| Author | Species | Approach/drug | Dosage | Administration | Plaque site |
Main findings in plaques |
|---|---|---|---|---|---|---|
| Badimon et al. 1990 22 |
Rabbit (New Zealandwhite rabbits) |
HDL-VHDL | 50 mg | i.v., weekly over 4 weeks |
Total aorta surface |
Extent of fatty streaks ↓ Aortic lipid accumulation (TC, FC and PL) ↓ |
| Parolini et al. 2008 84 |
Rabbit (New Zealandwhite rabbits) |
apoA-IMilano (ETC-216) |
1) 5 mg/kg 2) 10 mg/kg 3) 20 mg/kg 4) 40 mg/kg 5) 150 mg/kg |
5 i.v. injections, every 4 days |
Carotid arteries (assessed by IVUS and MRI) |
Atheroma volume ↓ with 3 highest dosages Significant regression after 2nd administration of 150 mg/kg |
| Shah et al. 2001 32 |
Mouse (apoE−/−) |
apoA-IMilano | 400 mg/kg | Single i.v. injection |
Aortic root (48 hours post injection) |
Lipid content ↓ Macrophage content ↓ |
| Cho et al. 2009 85 |
Mouse (apoE−/−) |
1) rHDL 2) V156K-rHDL (V156K point mutant of apoA-I) 3) R173C-rHDL (apoA-IMilano) |
120 mg/kg | Single i.v. injection |
Aortic root (24 and 48 hours post injection) |
Lipid content: rHDL↓, V156K ↓↓, R173C ↓↓ Macrophage content: rHDL ↓, V156K ↓↓, R173C ↓↓ |
| Feig et al. 2011 31 |
Mouse (apoE−/−) |
Aortic arch transplant into apoE−/− mice transgenic for human apoA-I |
Aortic arch (7 days post transplant) |
Plaque size ↓ Macrophage content ↓ M1 macrophages ↓ M2 macrophages ↑ CCR7 ↑ in plaque macrophages |
||
| Rayner et al. 2012 52 |
Mouse (LDLr−/−) |
Anti-miR33 | 10 mg/kg | 1st week: 2 s.c. injections, followed by weekly injections |
Aortic root (after 4 weeks of treatment) |
Plaque size ↓ Macrophage content ↓ Lipid content ↓ Collagen content ↑ M1 macrophages ↓ M2 macrophages ↑ |
| Nissen et al. 2003 58 |
Human (ACS) |
apoA-IMilano (ETC 216) |
1) 15 mg/kg 2) 45 mg/kg |
i.v., weekly over 5 weeks |
Coronary artery (assessed by IVUS) |
Combined rHDL groups vs. baseline (Median): - Change in total atheroma volume - 13.3 mm3 (p<0.001) - Change in atheroma volume: −4.2% - Change in percent atheroma volume (PAV): −0.81% (p=0.02) |
| Tardif et al. 2007 (ERASE) 59 |
Human (ACS) |
rHDL (CSL-111) | 1) 40 mg/kg 2) 80 mg/kg (80 mg/kg dosage discontinued due to liver function test abnormalities) |
i.v., weekly over 4 weeks |
Coronary artery (assessed by IVUS) |
rHDL vs. placebo group (Median): - Change in total plaque volume: − 5.3 mm3 vs. −2.3 mm3 (n.s.) - Change in atheroma volume: − 3.4% vs. −1.6% (n.s.) - Significant improvement of plaque characterization index and coronary score |
| Shaw et al. 2008 60 |
Human (PAD) |
rHDL (CSL-111) | 80 mg/kg | i.v. | SFA (after atherectomy 5–7 days post infusion) |
Lipid content ↓ Macrophages cell size ↓ VCAM-1 expression ↓ |
ACS = acute coronary syndrome; Anti-miR = anti-microRNA; ApoA-I = apolipoprotein A-I; apoE = apolipoprotein E; CCR7 = C-C chemokine receptor type 7; ERASE = Effect of rHDL on Atherosclerosis - Safety and Efficacy; FC = free cholesterol; HDL = high-density lipoprotein; i.v. = intravenous; IVUS = intravascular ultrasound; LDLr = low-density lipoprotein receptor; n.s.= non significant; MRI = magnetic resonance imaging; PAD = peripheral artery disease; PAV = percent atheroma volume; PL = phospholipids; rHDL = reconstituted high-density lipoprotein; s.c. = subcutaneous; SFA = superficial femoral artery; TC = total cholesterol; VCAM-1 = vascular cell adhesion molecule 1; VHDL = very-high-density lipoprotein.