Innate immunity and vein graft disease

Abstract

For proper functioning as a venous bypass graft, a venous conduit should become adapted to the arterial circulation. Proliferation of smooth muscle cells is a key element in the arterialization process, but also immune cells play a crucial role. Immune cells such as macrophages infi ltrate the vessel wall, and secrete cytokines and growth factors that enhance the process of vein graft arterialization. Later on, these infl ammatory cells act in a negative role since innate immune responses have been linked to vein graft failure. Cholesterol and oxidized low density lipoproteins (oxLDL) also trigger these responses resulting in the development of atherosclerotic lesions during advanced vein graft disease. Here we show the results of targeting members of the innate immune system such as toll-like receptors, the complement system, cytokines, mast cells, and natural killer (NK) cells. Targeted deletion of certain immune cells or genes encoding pro-infl ammatory factors results in decreased vein graft thickening in mouse models, whereas stimulation of infl ammatory responses accelerates it. New therapies are in development based on these concepts of involvement of the immune system in vein graft disease.