2013Conference PublicationsOpen access

Foam cell formation in atherosclerosis: HDL and macrophage reverse cholesterol transport

Shuai Zhang, L. R. Ritter, Akif Ibragimov

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Abstract

Macrophage derived foam cells are a major constituent of the fatty deposits characterizing the disease atherosclerosis. Foam cells are formed when certain immune cells (macrophages) take on oxidized low density lipoproteins through failed phagocytosis. High density lipoproteins (HDL) are known to have a number of anti-atherogenic effects. One of these stems from their ability to remove excess cellular cholesterol for processing in the liver---a process called reverse cholesterol transport (RCT). HDL perform macrophage RCT by binding to forming foam cells and removing excess lipids by efflux transporters. We propose a model of foam cell formation accounting for macrophage RCT. This model is presented as a system of non-linear ordinary differential equations. Motivated by experimental observations regarding time scales for oxidation of lipids and MRCT, we impose a quasi-steady state assumption and analyze the resulting systems of equations. We focus on the existence and stability of equilibrium solutions as determined by the governing parameters with the results interpreted in terms of their potential bio-medical implications.

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Macrophage derived foam cells are a major constituent of the fatty deposits characterizing the disease atherosclerosis. Foam cells are formed when certain immune cells (macrophages) take on oxidized low density lipoproteins through failed phagocytosis. High density lipoproteins (HDL) are known to have a number of anti-atherogenic effects. One of these stems from their ability to remove excess cellular cholesterol for processing in the liver---a process called reverse cholesterol transport (RCT). HDL perform macrophage RCT by binding to forming foam cells and removing excess lipids by efflux transporters. We propose a model of foam cell formation accounting for macrophage RCT. This model is presented as a system of non-linear ordinary differential equations. Motivated by experimental observations regarding time scales for oxidation of lipids and MRCT, we impose a quasi-steady state assumption and analyze the resulting systems of equations. We focus on the existence and stability of equilibrium solutions as determined by the governing parameters with the results interpreted in terms of their potential bio-medical implications.

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Available abstract

Macrophage derived foam cells are a major constituent of the fatty deposits characterizing the disease atherosclerosis. Foam cells are formed when certain immune cells (macrophages) take on oxidized low density lipoproteins through failed phagocytosis. High density lipoproteins (HDL) are known to have a number of anti-atherogenic effects. One of these stems from their ability to remove excess cellular cholesterol for processing in the liver---a process called reverse cholesterol transport (RCT). HDL perform macrophage RCT by binding to forming foam cells and removing excess lipids by efflux transporters. We propose a model of foam cell formation accounting for macrophage RCT. This model is presented as a system of non-linear ordinary differential equations. Motivated by experimental observations regarding time scales for oxidation of lipids and MRCT, we impose a quasi-steady state assumption and analyze the resulting systems of equations. We focus on the existence and stability of equilibrium solutions as determined by the governing parameters with the results interpreted in terms of their potential bio-medical implications.

Key concepts: Foam cell, Reverse cholesterol transport, Macrophage, Cholesterol, Efflux, Chemistry, ABCA1, Immune system

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