A robust rabbit model of human atherosclerosis and atherothrombosis

Abstract

Disruption and thrombosis of atherosclerotic plaques cause most acute cardiovascular events, but their systematic study has been hampered by the lack of suitable animal models. To assess the value of a modified rabbit model of atherothrombosis, we performed detailed histology of rabbit aortic plaques. Atherosclerosis was induced with a high cholesterol diet fed 2 weeks prior to and 6 weeks after balloon injury of the aorta, followed by 4 weeks of normal diet. We found six out of eight types of plaques cataloged by the American Heart Association in the rabbit aorta. Vulnerable plaques were defined as those with attached platelet and fibrin-rich thrombi after pharmacological triggering with Russellʼs viper venom and histamine. Ruptured plaques had, as also described for human plaques: i) marked medial and adventitial changes, including neovascularization and inflammation; ii) cholesterol monohydrate crystals and liquid crystalline cholesterol esters in the intima and the fibrous cap; and iii) inflamed, thin fibrous caps. Increased cholesterol monohydrate area, internal elastic lamina area, positive remodeling, fibrous cap inflammation, adventitia breakdown, and inflammation were independent predictors of plaque disruption. Our findings reveal novel insights into plaque vulnerability and could guide the design of noninvasive imaging approaches for detecting and treating high-risk plaques.-Phinikaridou, A., K. J. Hallock, Y. Qiao, and J. A. Hamilton. A robust rabbit model of human atherosclerosis and atherothrombosis. J. Lipid Res. 2009. 50: 787-797.

Regions of Low Endothelial Shear Stress Colocalize With Positive Vascular Remodeling and Atherosclerotic Plaque Disruption

“…This model was initially used for the detection of mural thrombus formed after plaque disruption by in vivo MRI without 34 and with a fibrin contrast agent. 35 Most recently, we have shown the histological similarities between rabbit and human plaques, 33 and the ability of in vivo MRI measurements to predict plaque with a higher likelihood of disruption.…”

“…Various flow data can be extracted from the acquired images, including velocity profiles, flow rates, shear rate, and shear stress. 21,29,30 In this study, we have used in vivo MRI in a rabbit model of atherosclerosis and controlled plaque disruption [31][32][33] to investigate whether low values of ESS associate with plaque burden, vascular remodeling, and plaque disruption. This model was initially used for the detection of mural thrombus formed after plaque disruption by in vivo MRI without 34 and with a fibrin contrast agent.…”

“…28,[31][32][33][34][35] Briefly, rabbits were fed a 1% cholesterol diet (PharmaServe, MA) for 2 weeks before and 6 weeks after balloon injury of the abdominal aorta, followed by 4 weeks of normal chow diet. Denudation of the aortic wall was performed under general anesthesia (acepromazine [0.75 mg/kg IM], ketamine [35 mg/kg, IM], and xylazine [2.5 mg/kg, IM]).…”

“…Therefore, the aorta between the renal branches, right below the diaphragm, and the iliac bifurcation was denudated covering a length of ≈9 to 10 cm. 28,[31][32][33][34][35] Pharmacological triggering of thrombosis was induced with Russell viper venom (0.15 mg/kg IP; Enzyme Research, IN), a procoagulant factor followed 30 minutes later by histamine, a vasoconstrictor in rabbits (0.02 mg/kg IV; Sigma-Aldrich, MO). This procedure was performed twice within a 48-hour period.…”

An experimental study on MR imaging of atherosclerotic plaque with SPIO marked endothelial cells in a rabbit model

“…It is generally believed that injuries of the intima can lead to the dysfunction of vascular endothelial cells (17). The combination of lipidosis and endothelial cell .…”