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. 2019 Aug 15;11(8):4614–4633.

Table 2.

Genetic porcine models available for the atherosclerosis research

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.