Table 1.
Animal studies supporting HO-1 antiatherogenic role.
| Study/References | Experimental model | HO-1 modulation | Findings |
|---|---|---|---|
| Ishikawa et al. (2001a) | Watanabe rabbits on a chow diet | SnPPIX (−) | I.P. SnPPIX 5×/week for 5 weeks inhibited aortic HO activity, increased plasma, aortic, and liver lipoperoxides and enhanced aortic atherosclerotic plaques (en face) by 155% as compared with controls. |
| Ishikawa et al. (2001b) | LDL-R−/− mice fed a chow diet or HFD | Hemin (+) SnPPIX (−) | I.P. hemin or hemin + deferoxamine 4×/week for 6 weeks induced aortic HO-1 and decreased aortic root lesions. I.P. SnPPIX decreased aortic HO activity and enhanced lesions as compared with controls. |
| Juan et al. (2001) | ApoE−/− mice fed a chow diet | I.V. Adv HO-1 vs. L.V. Adv HO-1 | I.V. Adv HO-1 for 1 week increased liver and aortic HO-1 and enhanced aortic root lesions while L.V. Adv HO-1 failed to increase aortic HO-1 and did not affect lesion formation as compared with controls. Similar findings in 14-week and 20-week old mice. |
| Yet et al. (2003) | HO-1−/−ApoE−/− vs. HO-1+/+ ApoE−/− mice on a HFD for 8 weeks | Genetic deletion of HO-1 | 12-week-old HO-1−/−ApoE−/− mice, fed 8 weeks on HFD developed increased atherosclerotic lesions in the right brachiocephalic arteries by ~260% as compared with HO-1+/+, ApoE−/− controls. |
| Orozco et al. (2007) | Bone marrow transplantation of HO-1−/− vs. HO-1+/+ into LDL-R−/− mice fed a HFD | Genetic deletion of HO-1 in bone marrow-derived cells | Sublethally irradiated LDL-R−/− mice reconstituted with HO-1−/− bone marrow developed aortic root plaques with greater macrophage content than control mice reconstituted with HO-1+/+ bone marrow. HO-1 expression decreased generation of foam cells in macrophages. |
| Cheng et al. (2009) | ApoE−/− mice fed a HFD diet, with a cast around right carotid artery for 9 weeks | CoPPIX (+) ZnPPIX (−) | I.P. CoPPIX for 3 weeks increased relative cap thickness and decreased necrotic core/intima ratio while ZnPPIX resulted in the opposite despite no effects on plaque burden, suggesting that HO-1 promotes plaque stability. |
| Li et al. (2011) | New Zealand White Rabbits fed a HFD, subjected to balloon-induced aortic injury | hemin (+) SnPPIX (−) | I.P. hemin every other day for 12 weeks decreased intimal area positive for macrophages, lipids by 35 and 43% respectively, but increased intimal SMCs and collagen by 100 and 42% respectively. SnPPIX resulted in opposite results. Hemin decreased apoptosis and MMP-9 expression while SnPPIX resulted in the opposite. |
| Liu et al. (2012) | New Zealand White Rabbits, fed a chow diet and HFD | hemin (+) ZnPPIX (−) | I.P. ZnPPIX everyday for 12 weeks increased plaque area by 19% while hemin led to a threefold decrease in plaque area vs. controls fed a HFD. Hemin increased CO generation and decreased eNOS activity and NO tissue levels. |
HFD, high fat diet, I.V., intravenous, L.V., left ventricular, I.P., intraperitoneal, Adv, adenoviral.