Table 2.
Model type | Advantages | Disadvantages | Utility | References |
---|---|---|---|---|
Tg D374Y-PCSK9 minipigs | Develop moderate hypercholesterolemia and human-like atherosclerosis on the standard low-fat diet | The high-fat diet required to develop severe hypercholesterolemia and advanced atherosclerosis | Useful for testing different imaging techniques from 12 months of age. | [12,122,130-132] |
Acquire reduced hepatic LDLR levels | Multiple expression of the mutant transgene may limit the utility for treatments designed to increase LDLR expression or reduce PCSK9 activity | |||
Impaired LDL clearance | ||||
LDLR-/- minipigs | Develop advanced human-like atherosclerosis, including coronary lesions | The high-fat diet required | Suitable for coronary atherosclerosis research, development of plaque stabilization drugs and percutaneous diagnostic and interventional devices | [130,133,148] |
ApoE-/- minipigs | Develop moderate cholesterolemia and atherosclerosis on the low-fat diet | The high-fat diet required to develop prominent human-like dyslipidemia and progressive atherosclerosis | Suitable for translational studies of atherosclerosis | [136,137] |
ApoE /LDLR double KO minipigs | Develop atherosclerosis-related lipid metabolism | Validation of atherosclerosis phenotype is limited possibly due to the fact that in-frame mutations in both the ApoE and LDLR alleles may give rise to truncated ApoE and LDLR proteins with the partially retained function | Useful for studies determining the function of genes involved in the progression of human atherosclerosis | [138] |
Note: Tg D374Y-PCSK9 minipigs - Transgenic D374Y-PCSK9 minipigs; LDLR - low-density lipoprotein receptor; LDL - low-density lipoprotein; LDLR-/- - low-density lipoprotein receptor deficient; ApoE-/- - apolipoprotein E deficient; ApoE/LDLR double KO minipigs - apolipoprotein E and low-density lipoprotein receptor double knockout minipigs.