An oxidized lipid-peroxisome proliferator-activated receptor gamma-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 gamma. 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 gamma-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.
Barlic
Jana
J
Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Murphy
Philip M
PM
D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology*; D002448:Cell Adhesion; D018932:Chemokine CCL2 / Q000502:physiology; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000502:physiology; D003331:Coronary Vessels / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology; D006801:Humans; D008077:Lipoproteins, LDL / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D009000:Monocytes; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D047495:PPAR gamma / Q000502:physiology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018160:Receptors, Cytoplasmic and Nuclear
D018932:Chemokine CCL2; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008077:Lipoproteins, LDL; D047495:PPAR gamma; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018160:Receptors, Cytoplasmic and Nuclear; C099252:oxidized low density lipoprotein