Atherosclerosis chemokines role

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... 

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. 

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

Lucas AD, Greaves DR. Atherosclerosis role of chemokines and macrophages. Expert Rev Mol Med 2001 2001 1-18. 

Fig. 5. Scavenger receptors (SRs). Structural features of scavenger receptors with proposed roles in atherosclerosis. The plasma membrane or the endosomal membrane (for CD68, which is mainly found in the endosomal compartment) is indicated by the vertical line, with the cytoplasmic domains to the left. The individual structural domains are described in the box. SRCL, SR with C-type lectin MARCO, macrophage receptor with collagenous structure SREC, SR expressed by endothelial cells SR-PSOX/CXCL16, membrane-bound chemokine L16 other SRs are described in the text (Section 7). Not drawn to scale.

Extensive research has been performed in mice to determine the factors involved in the pathogenesis of atherosclerosis (see Table 6.7). Two knock-out mouse strains were used apolipoprein E (ApoE ) mice that develop spontaneous atherosclerosis that progresses to myocardial infarction and stroke and LDL receptor (Ldlr ) mice that develop hypercholesterolemia and lesion development upon fat feeding [175]. Crossbreeding of this mice with mice that carry deletions in genes of the immune system indicate an essential role of chemokines and their receptors in the early phase of atherosclerosis (for excellent reviews, see [176, 177]). 

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