Table 3.
Experimental Therapeutic Approach Targeting Iron in Cardiovascular Disease
| Approach | Atherosclerosis phenotype | Treatment or model | Similarities and Differences | References |
|---|---|---|---|---|
| Iron restriction by reduced dietary iron | Reduced Increased plaque stability |
(i) Low-iron diet (3 months), reduced serum Ft (ii) Low-iron diet (4/8 months) in iron-loaded ApoE-nullFPNwtC/326S mice, reduced Tf sat |
(i, ii) ApoE-null background, elevated plaque collagen and reduced MMP9, reduced arterial and plaque iron deposition and lipid core (iii) ApoE-null background, reduced arterial iron, plaque inflammation, and endothelial dysfunction |
(i) (126) (ii) (127) (iii) (232) |
| Iron restriction by chelation | Reduced Decreased inflammation and vascular dysfunction |
(i) Deferoxamine (ip, 100 mg/kg, 10 weeks) (ii) Deferoxamine (ip, 72 mg/kg/day, 5 days/week, 12 weeks) (iii) Desferricoprogen (ip, 160 mg/kg/every 2 days, 8 weeks) (iv) Deferasirox (oral, 150 mg/kg/day, 4/8 months) in iron-loaded ApoE-nullFPNwtC/326S mice, reduced Tf sat |
(i) ApoE-null background, Western diet, reduced macrophages, and arterial inflammatory cytokines (ii) Rabbits, high cholesterol diet, reduced lesion size (iii) ApoE-null background, high-fat diet, reduced lipid oxidation, foam cells, and endothelial activation (iv) ApoE-null background, standard diet, reduced arterial iron, plaque inflammation, and endothelial dysfunction |
(i) (256) (ii) (144) (iii) (168) (iv) (232) |
| Hepcidin inhibition | Reduced Improved plaque macrophage phenotype |
(i) LDN-193189 (ip, 10 mg/kg, 10 weeks) (ii) BMP ligand trap ALK3-Fc (ip, 2 mg/kg/every 2 days, 6 weeks) (iii) Transgenic mouse model overexpressing BMP signaling antagonist MGP |
(i) ApoE-null background, high-fat diet, decreased foam cell formation, improved macrophage cholesterol efflux (ii) Ldlr-null background, Western diet, reduced plaque macrophages (iii) ApoE-null background, standard and high-fat diet, reduced calcification, and inflammation |
(i) (185) (ii) (60) (iii) (243) |
| HO-1 induction | Reduced | (i) Bach-1-null mice (ii) HO-1 overexpression by intraventricular Adv-HO-1 (iii) HO-1 induction by cobalt protoporphyrin |
(i) ApoE-null background, high-fat diet, vascular HO-1 upregulation (ii) ApoE-null background, standard diet, reduced arterial iron (iii) Model of vulnerable plaque by carotid cast, ApoE-null background, Western diet, reduced necrotic core and plaque lipid, increased VSMCs and cap thickness |
(i) (237) (ii) (105) (iii) (44) |
Approach, atherosclerosis phenotype, treatment or genetic manipulation, similarities and differences of animal models used to study the therapeutic benefit of iron targeting in CVD.
BMP, bone morphogenetic protein; MGP, matrix Gla protein.