An Oxidized Lipid–Peroxisome Proliferator-Activated Receptor γ–Chemokine Pathway in the Regulation of Macrophage-Vascular Smooth Muscle Cell Adhesion

Recent genetic studies have implicated pro-inflammatory chemokines and chemokine receptors in atherogenesis. Studies at the molecular and cellular levels have suggested specific atherogenic mechanisms for two chemokine-chemokine receptor pairs, CCL2-CCR2 and CX3CL1-CX3CR1, involving differential receptor regulation by the transcription factor peroxisome proliferator-activated receptor γ . This pathway is triggered by oxidized proatherogenic lipids, such as oxidized low-density lipoprotein and linoleic acid derivatives, which promote differentiation of CCR2 hi CX3CR1 lo human monocytes to CCR2 lo CX3CR1 hi macrophages that adhere to coronary artery smooth muscle cells in a CX3CR1- and peroxisome proliferator-activated receptor γ -dependent manner. Switching CX3CR1 on and CCR2 off in vivo may result in cessation of CCR2-dependent migration and activation of CX3CR1-dependent retention that together may promote foam cell accumulation in the vessel wall.