Abstract-Activated resident macrophages sustain atheroma, and a high macrophage content is associated with plaque vulnerability. Factors leading to differentiation and activation of these blood-derived cells remain largely uncharacterized.We investigated the contribution of interaction with collagen type I, the predominant component of atherosclerotic matrix, to differentiation and modulation of characteristic macrophage functions, including intracellular lipid accumulation and production of the typical matrix-degrading enzyme matrix metalloproteinase (MMP)-9.