Replacing dietary carbohydrate with protein and fat decreases the concentrations of small LDL and the inflammatory response induced by atherogenic diets in the guinea pig

Guinea pigs resemble humans in cholesterol and lipoprotein metabolism; however, there is limited information on the vascular inflammatory response with induction of atherosclerosis in this animal model. The purpose of this study was to document a vascular inflammatory response associated with dietary-induced atherosclerosis in the guinea pig and determine the effect of replacing dietary carbohydrate with protein and fat on this response. Thirty male Hartley guinea pigs were randomly assigned to a high dietary cholesterol, high-carbohydrate (HC); a high-cholesterol, low-carbohydrate (LC) or a control (CON) diet for 12 weeks. Analysis of cytokine protein expression [interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and GM-CSF) and m RNA expression (IFN-γ, TNF-α, IL-1β, MCP-1 and IL-8] were performed along with the measurement of cholesterol concentration in the aorta, plasma lipids and plasma low-density lipoprotein subfractions. There was a similar and significant accumulation of cholesterol in the thoracic aorta in the HC and LC groups compared to the CON group. Aortic cytokine protein expression (TNF-α, IFN-γ and IL-6) and m RNA expression (TNF-α and IFN-γ) were significantly elevated in both high-cholesterol fed groups (HC and LC) (P<.05) compared to the CON group. Compared to the HC group, animals fed the LC diet had reduced protein and m RNA TNF-α expression, as well as a reduced concentration of small LDL particles in the plasma. This study is the first to document a dietary cholesterol-induced vascular inflammatory response in guinea pigs that is partially regulated by the macronutrient content of the diet. Guinea pigs may be a useful animal model to evaluate the cellular and molecular components of atherosclerosis.