Mouse Models of Coronary Artery Atherosclerosis

Review Article

J Cardiovasc Disord. 2016; 3(1): 1021.

Mouse Models of Coronary Artery Atherosclerosis

Gonzalez L1,2, Yu P1,2 and Trigatti BL1,2*

1Department of Biochemistry and Biomedical Sciences, McMaster University, Canada

2Thrombosis and Atherosclerosis Research Institute, McMaster University, Canada

*Corresponding author: Bernardo Trigatti, Department of Biochemistry and Biomedical Sciences, and Thrombosis and Atherosclerosis Research Institute, McMaster University, Canada

Received: July 25, 2015; Accepted: January 18, 2016; Published: January 20, 2016


Atherosclerosis is a chronic disease affecting large- and medium-sized arteries and it is the main underlying cause of cardiovascular diseases. Animal models, particularly mouse models, represent powerful tools to uncover disease mechanisms. Through a combination of genetic and diet manipulation, several mouse models for atherosclerosis research have been developed, with the apolipoprotein E and low-density lipoprotein receptor models being the most widely used. However, these mouse models remain relatively resistant to atherosclerosis development in coronary arteries and development of atherosclerosis related myocardial infarction, key features of human atherosclerotic disease. The discovery that the scavenger receptor class B type 1 acted as a high affinity high-density lipoprotein receptor and the inactivation of its gene in mice allowed for the generation of new models exhibiting either spontaneous or diet-induced occlusive coronary artery atherosclerosis and myocardial infarction. This review will discuss mouse models of coronary heart disease, highlighting their characteristics and focusing on those dependent on scavenger receptor class B type 1 deficiency.

Keywords: Atherosclerosis; Mouse; Coronary arteries


APO: Apolipoprotein; APOBEC-1: apoB mRNA Editing Catalytic Polypeptide-1; CA: Coronary Artery; CAD: Coronary Artery Disease; CVD: Cardiovascular Disease; DKO: Double Knockout; eNOS: Endothelial Nitric Oxide Synthase; HDL: High-Density Lipoprotein; HDL-C: HDL Cholesterol; HL: Hepatic Lipase; ICAM: Intercellular Adhesion Molecule; IDL: Intermediate-Density Lipoprotein; KO: Knockout; LDL: Low-Density Lipoprotein; LDLR: LDL Receptor; LRP: LDLR-Related Protein; PDZ: Postsynaptic Density Protein-95, Drosophila disc-large protein, Zonula occludens protein 1; PDZK1, PDZ Containing 1; Plg: Plasminogen; SMC: Smooth Muscle Cells; SR-B1: Scavenger Receptor Class B Type 1; Tg: Transgenic; tKO: triple Knockout; TNF: Tumor Necrosis Factor; uPA: urokinase Plasminogen Activator; VCAM: Vascular Adhesion Molecule; VLDL: Very Low-Density Lipoprotein


Despite the great advances in cardiovascular research in the past decades, Cardiovascular Disease (CVD) remains the main cause of death in western societies [1,2]. In the year of 2012, about 15.5 million US adults had CVD, among which 7.6 million were diagnosed with myocardial infarction [3]. It has been estimated that in the US only, 40.5 % of the population will present some form of CVD by 2030 [4]. Alongside the increase in the prevalence of CVD worldwide, the cost associated with the treatment of these conditions also increases dramatically. The medical cost associated with the treatment of Coronary Artery Disease (CAD) in the US is projected to increase by approximately 200 % in a span of 20 years [5]. Hence, efforts are concentrated on understanding and characterizing the several factors that govern the initiation and progression of CAD. Atherosclerosis, the main underlying pathology in CAD, is a chronic inflammatory disease of the artery wall that affects large- and medium-sized arteries [1]. The presence of early-stage atherosclerotic lesions (intima-media thickening) can be detected in young adults (adolescence), and the bulk of the disease develops during adulthood [6,7].

Atherosclerosis is characterized by the accumulation of modified lipoproteins in the intimal layer of the vessel wall, which triggers the expression of adhesion molecules on the surface of the endothelium (Figure 1) [8]. In addition to the expression of adhesion molecules, the endothelial cells can also release chemokines triggering the recruitment, from circulation, of immune cells, mainly monocytes that will differentiate into macrophages [9]. These mononuclear phagocytes can now ingest the aggregated modified lipoproteins becoming foam cells. Lipid-laden macrophage foam cells may further contribute to the pro-inflammatory environment in the vessel wall by releasing cytokines like interleukin-1β and Tumor Necrosis Factor (TNF)-a [2,10]. The formation of the atherosclerotic plaque also involves the recruitment and activation of Smooth Muscle Cells (SMC) from the tunica media into the intima. Recruited SMC secrete extracellular matrix proteins, like collagen and elastin, and accumulate on top of the lesion generating the fibrous cap [11]. Foam cells, cell debris and extracellular lipid accumulate underneath the fibrous cap generating the pro-thrombotic necrotic core. The rupture of the fibrous cap, and exposure of the contents of the lipidrich necrotic core to blood, trigger thrombus formation leading to myocardial infarction/stroke [12].

Citation: Gonzalez L, Yu P and Trigatti BL. Mouse Models of Coronary Artery Atherosclerosis. J Cardiovasc Disord. 2016; 3(1): 1021. ISSN: 2379-7991