C-reactive protein (CRP) is present in the atherosclerotic plaques and appears to promote atherogenesis. Intraplaque CRP colocalizes with oxidized low-density lipoprotein (ox-LDL) and macrophages in human atherosclerotic lesions . MMP-9 has been implicated in plaque rupture.
C-reactive protein (CRP) promotes ox-LDL uptake and MMP induction in vitro, however, these have not been investigated in vivo. We examined the effect of CRP on ox-LDL uptake and MMP-9 production in vivo in Wistar rats. C-Reactive Protein CRP significantly increased ox-LDL uptake in the peritoneal and sterile pouch macrophages compared to human serum albumin (huSA). CRP also significantly increased intracellular cholesterol ester accumulation compared to huSA . The increased uptake of ox- LDL by CRP was inhibited by pretreatment with antibodies to CD32, CD64, CD36 and fucoidin, suggesting uptake by both scavenger receptors and Fc gamma receptors.
Furthermore, CRP treatment increased MMP-9 activity in macrophages compared to huSA, which was abrogated by inhibitors to p38MAP kinase, ERK and NFKb, but not JNK prior to hCRP treatment. Since ox-LDL uptake by macrophages contribute to foam cell formation and MMP release to plaque instability, this study provides novel in-vivo evidence for the role of CRP in atherosclerosis.
J Lipid Res. 2008 Feb 2
