Pressure overload leads to coronary plaque formation, progression, and myocardial events in ApoE-/- mice

Area of Science:

• Cardiovascular Research
• Animal Models of Disease
• Atherosclerosis Pathogenesis

Background:

• Hypercholesterolemia and hypertension are key risk factors for coronary artery disease (CAD), a leading cause of death.
• Existing animal models fail to replicate critical aspects of human CAD, such as plaque rupture and myocardial infarction.
• Transverse aortic constriction (TAC) in ApoE-/- mice has shown potential for inducing coronary lesions.

Purpose of the Study:

• To characterize the extent and location of coronary lesions following TAC in ApoE-/- mice.
• To evaluate the susceptibility of these coronary plaques to disruption and subsequent myocardial events.
• To establish a more accurate mouse model for studying human coronary artery disease.

Main Methods:

• ApoE-/- mice underwent transverse aortic constriction (TAC) surgery.
• Coronary lesions, stenosis, and plaque characteristics were analyzed post-TAC.
• Incidence of myocardial events, including thrombosis and occlusion, was assessed.

Main Results:

• Approximately 90% of ApoE-/- mice developed coronary lesions after TAC.
• Left anterior descending artery lesions and stenosis (59%) were commonly observed.
• Myocardial events occurred in 74% of mice, primarily driven by plaque thrombosis and occlusion.

Conclusions:

• TAC in ApoE-/- mice reliably induces coronary lesions and progression, closely resembling human CAD.
• This model offers a valuable tool for investigating CAD development, plaque vulnerability, and therapeutic strategies.
• The model's ability to recapitulate thrombosis and myocardial infarction enhances its relevance for translational research.