Title

Confirmation of the guinea pig as an experimental model of inflammation with dietary-induced atherosclerosis

Date of Completion

January 2005

Keywords

Health Sciences, Nutrition|Health Sciences, Recreation

Degree

Ph.D.

Abstract

Inflammation plays a major role in the development of atherosclerotic vascular disease through its diverse affects on arterial wall biology and lipoprotein metabolism. Inflammatory cells are a prominent feature of atherosclerotic lesions, both in humans and cholesterol-fed animal models of atherosclerosis. Given the critical nature of inflammation, an ideal animal model of atherosclerosis should have a resemblance to the human disease in terms of both cholesterol and lipoprotein metabolism and the inflammatory process. The primary aim of this study was to develop the guinea pig as an experimental animal model of inflammation in dietary-induced atherosclerosis. A secondary aim was to compare the effects of a high-cholesterol diet either high or low in carbohydrate on inflammatory markers. Thirty male Hartley guinea pigs were randomly assigned to one of three diet treatments for 12 wk (Low-Cholesterol, High-Cholesterol/High-Carbohydrate and High-Cholesterol/Low-Carbohydrate Groups). Animals were euthanized after 12 weeks and blood samples taken for determination of plasma lipids and serum total ketone bodies. The aorta was dissected and separated into three sections for measurement of cytokine protein concentrations (INF-γ, TNF-α, IL-1β, IL-6 and GM-CSF), mRNA expression (IFN-γ, TNF-α, IL-1β, MCP-1 and IL-8) and cholesterol concentration in the aorta. There was a significant increase in all cytokine protein concentrations in the high-cholesterol/high-carbohydrate group compared to the low-cholesterol group. The high-cholesterol/low-carbohydrate group also demonstrated a significant increase in all cytokine protein concentrations except GM-CSF. Real-time RT-PCR showed a significant increase in the expression of IFN-γ and TNF-α mRNA for both high-cholesterol groups compared to the low-cholesterol group. This study is the first to confirm that guinea pigs do demonstrate an increased vascular inflammatory response after the intake of an atherogenic diet. This novel finding is important as it will allow for the use of guinea pigs in future studies by where a system-wide animal model can be evaluated for the cellular and molecular components involved in the immunomodulation of atherosclerosis. ^