Animals | Methods | Advantages | Disadvantages |
Large-animal models | |||
Rhesus monkeys31 | Genetic LDL receptor deficiency; low-fat diet | Plaque in coronary arteries; spontaneous plaque rupture; evidence of fibrinogen/fibrin in plaques | Restricted availability; ethical issues |
Göttingen miniature pigs32 | 2% cholesterol feeding; balloon injury; irradiation; intracoronary injection of serotonin | Intraplaque haemorrhage | Difficult manipulation; rupture not spontaneous |
Pigs with inherited hypercholesterolaemia34 | Mutant apolipoproteins B and U; low-fat diet | Plaques in coronary arteries; spontaneous plaque rupture; intraplaque haemorrhage | Long-term experiment; restricted availability |
Pigs35 | Percutaneous injection of cholesteryl linoleate into the arterial wall | Complex lesions in the injected arteries; short experimental time | Rupture not spontaneous; difficult manipulation |
Rabbits37 | High-fat diet; balloon injury; pharmacological triggering with RVV and histamine | Plaque rupture; overlying platelet-rich thrombi | Rupture not spontaneous |
Watanabe heritable hyperlipidaemic rabbits38 | Treatment with RVV and serotonin/angiotensin II | Accelerated aortic thrombosis | Rupture not spontaneous; aortic medial necrosis |
Rabbits17 | high-fat diet; balloon injury; p53 gene local transfection; RVV and histamine triggering | Extensive SMC apoptosis and active inflammation in fibrous caps; high rate of plaque rupture and luminal thrombosis | Rupture not spontaneous |
Rabbits39 | High-fat diet; balloon injury; intraplaque balloon inflating | Plaque fissuring | Artificial rupture |
Rabbits41 | High-fat diet; perivascular electrical injury at the common carotid artery | Large, macrophage-rich and lipid-rich soft plaques | Rupture not reported |
Rabbits4243 | High-fat diet; balloon injury in the iliac artery; radiation | Macrophages and metalloproteinase-rich and SMC-lacking plaques | Rupture not spontaneous; difficult manipulation |
Rabbits2325 | High-fat diet; balloon injury; injection of erythrocytes into plaques | Plaques with abundant macrophage infiltration and lipid content; intraplaque haemorrhage and plaque rupture | Rupture not spontaneous |
Small-animal models | |||
ApoE−/− mice47 | High-fat diet; constrictive collar around carotid arteries; IL-18 gene systematic transfection | Plaques with markedly decreased intimal collagen contents; intraplaque haemorrhage | Rupture not reported |
ApoE−/− mice50 | High-fat diet; constrictive collar around carotid arteries; MMP-9 gene local transfection | Neo-angiogenesis; intraplaque haemorrhage | Rupture not reported |
ApoE−/− mice52 | High-fat diet; constrictive collar around carotid arteries; FasL gene local transfection | Plaques with increased SMC apoptosis of fibrous caps | Rupture not reported |
ApoE−/− mice53 | High levels of endogenous angiotensin II caused by clipping kidney arteries | Aortic plaques with enhanced inflammation | Rupture not reported |
ApoE−/− mice54 | Ligation of the carotid arteries; constant angiotensin II administration for 4 weeks | Plaques with enhanced inflammation; increased intraplaque haemorrhage associated with neovasculature | Rupture not reported |
ApoE−/− mice21 | High-fat diet; constrictive collar around carotid arteries; p53 gene local transfection; phenylephrine triggering | Increased cell apoptosis in fibrous caps; high rate of plaque rupture | Rupture not spontaneous |
ApoE−/− × LDLR−/− mice5556 | High-fat diet; hypoxic or mental stress stimulation | Advanced plaques in the coronary arteries; intraplaque haemorrhage; luminal thrombosis | Rupture not spontaneous; long-term experiment; high mortality rate |
ApoE−/− mice30 | High-fat diet; constrictive collar around carotid arteries; lipopolysaccharide treatment; mental stress stimulation | Plaques with thin fibrous caps, large lipid core and intensive inflammation; hyperhaemodynamic state | Rupture not spontaneous |
ApoE−/− mice40 | High-fat diet; forceps induced aortic injury | Plaque rupture associated with platelet-fibrin rich thrombi | Artificial rupture |
ApoE−/− mice61 | High-fat diet | Spontaneous plaque rupture and thrombosis of the aortic and coronary arteries | Long-term experiment; low rate of plaque rupture |
ApoE−/− mice62 | Chow diet | Spontaneous plaque rupture and intraplaque haemorrhage of the brachiocephalic arteries | Long-term experiment; low rate of plaque rupture |
ApoE−/− mice63 | High-fat diet | Spontaneous plaque rupture and thrombosis of the brachiocephalic arteries | Long-term experiment; low rate of plaque rupture |
ApoE−/− mice64 | High-fat diet | Spontaneous plaque rupture; increase in buried and thin fibrous caps | Long-term experiment; low rate of thrombosis |
ApoE−/− mice29 | High-fat diet | Spontaneous plaque rupture and thrombosis of the brachiocephalic arteries | Low rate of thrombosis |
IL-18, interleukin-18; LDL, low-density lipoprotein; MMP-9, matrix metalloproteinase-9; RVV Russell’s viper venom; SMC smooth muscle cell.