Chemokines atherosclerosis

Key Words Atherosclerosis chemokine chemokine receptor inflammation animal model CCR2 MCP-1 CX3CR1 fractalkine. 

Current evidence suggests that PPAR activation may limit inflammation and hence atherosclerosis. Both PPAR-a and PPAR-y can reduce T-cell activation, as shown by decreased production of EFN-y. PPAR-a agonists also rqness endothelial VCAM-1 expression and inhibit the inflammatory activation of vascular SMCs, while PPAR-y agonists repress endothelial chemokine expression and decrease macrophage MMP production. 

Chemokines have been shown to be associated with a number of autoinflammatory diseases including multiple sclerosis, rheumatoid arthritis, atherosclerosis, dermatitis, and organ transplant rejection. Evidence, reviewed below, is mounting that chemokines may play a major role in the pathophysiology of these diseases and thus chemokine receptor antagonists could prove to be useful therapeutics in treating these and other proinflammatory diseases. 

Boring L, Gosling J, Cleary M, Charo IF. Decreased lesion formation in CCR2 / mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 1998 394 894-7. 

Thus, inflammatory factors play a role at all stages of atherosclerosis in its initiation, progression, and final clinical manifestations. This new understanding of the pathophysiology of atherosclerosis has partly resulted from the study of chemokines and their receptors (4). 

The basic biology of chemokines and their receptors is well covered in Chapters 2 and 3 of this book, and we will focus hereafter upon the roles of individual chemokines and receptors in atherosclerosis. The largest amount of data on the roles of chemokines in cardiovascular disease (C VD) has been obtained from in vitro studies and murine models, which will be discussed in detail. In man, genetic polymorphisms in chemokine and chemokine-receptor genes have pointed to an important role for specific chemokines in various atherosclerotic diseases including coronary artery disease and carotid artery occlusive disease. For properties see Table 1. 

Our understanding of atherosclerosis as an inflammatory process has made great strides in the past decade, and it is clear from animal studies as well as clinical data that chemokines play an important role in atherosclerotic vascular... 

Dawson TC, Kuziel WA, Osahar TA, Maeda N. Absence of CC chemokine receptor-2 reduces atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis 1999 143(1) 205—211. 

McDermott DH, Halcox JP, Schenke WH, et al. Association between polymorphism in the chemokine receptor CX3CR1 and coronary vascular endothelial dysfunction and atherosclerosis. Circ Res 2001 89(5) 401—407. 

Bursill CA, Channon KM, Greaves DR. The role of chemokines in atherosclerosis recent evidence from experimental models and population genetics. Curr Opin Lipidol 2004 15(2) 145-149. 

Weber C. Platelets and chemokines in atherosclerosis partners in crime. Circ Res 2005 96(6) 612-616. 

Terkeltaub R, Boisvert WA, Curtiss LK. Chemokines and atherosclerosis. Curr Opin Lipidol 1998 9(5) 397—405. 

Shin WS, Szuba A, Rockson SG. The role of chemokines in human cardiovascular pathology enhanced biological insights. Atherosclerosis 2002 160(1) 91-102. 

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