Atherosclerosis chemokines expression

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. 

Burke-Gaffney A, Brooks AV, Bogle RG. Regulation of chemokine expression in atherosclerosis. Vascul Pharmacol 2002 38(5) 283-292. 

Pattison JM, Nelson PJ, Huie P, Sibley RK, Krensky AM. RANTES chemokine expression in transplant-associated accelerated atherosclerosis. J Heart Lung Transplant 1996 15 1194-1199. 

In an animal model of atherosclerosis E2 restores FasL expression, which is suppressed by atherogenic levels of serum cholesterol (328). High levels of Hey diminish with estrogen (reviewed in ref. 329). In HUVEC, E2 caused a decrease in expression of the NADPH oxidase subunit gp91phox, up-regulated eNOS expression, and inhibited the increase in adhesion molecule and chemokine expression in cells exposed to cyclic strain. Cyclic strain enhanced endothelial 02 formation, thereby offsetting the inhibitory effect of NO on the expression of these gene products (330). 

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.

As described before, chemokine inhibition may be a useful approach for the prevention of restenosis after coronary surgery or atherosclerosis. This concept has been further substantiated in vivo through the use of the broad spectrum vCKBP M3. Thus, systemic M3 expression from a transgene, or delivery of recombinant M3 protein, have been shown to reduce intimal hyperplasia after femoral artery injury [40] and aortic allograft transplantation [25], respectively. 

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