Animal models of atherosclerosis

Area of Science:

• Cardiovascular Research
• Animal Models of Disease
• Atherosclerosis Pathophysiology

Background:

• An ideal animal model for atherosclerosis research should mimic human anatomy and disease progression.
• Current models often rely on diet, genetic manipulation, or added risk factors, with mice and rabbits being common.
• Key features like plaque rupture and myocardial infarction remain challenging to replicate consistently.

Purpose of the Study:

• To identify and validate an animal model that accurately reflects human atherosclerosis pathophysiology.
• To establish a model suitable for pre-clinical evaluation of plaque-stabilizing therapies.

Main Methods:

• Review of existing animal models for atherosclerosis, including mice, rabbits, pigs, and non-human primates.
• Focus on genetic manipulation, such as Apolipoprotein E deficient (ApoE-/-) and LDL-receptor (LDLr) knockout mice.
• Evaluation of the ApoE-/-Fbn1C1039G+/- mouse model for its ability to consistently reproduce critical atherosclerotic events.

Main Results:

• Mice are predominant due to rapid reproduction and ease of genetic manipulation.
• Specific mouse models like ApoE-/- and LDLr knockout mice are widely used.
• The ApoE-/-Fbn1C1039G+/- mouse model consistently demonstrates intra-plaque microvessels, hemorrhages, spontaneous plaque ruptures, myocardial infarction, and sudden death.

Conclusions:

• The ApoE-/-Fbn1C1039G+/- mouse model offers a validated platform for pre-clinical studies.
• This model is particularly useful for evaluating novel plaque-stabilizing drugs due to its comprehensive replication of human disease features.
• Further research can leverage this model to advance atherosclerosis treatment strategies.