Although there is a well-established relationship between plasma C-reactive protein (CRP) levels and the risk of future cardiovascular disease (CVD), few in vivo studies have outlined the mechanisms underpinning the atherogenic role of CRP. Because oxidized LDL (oxLDL) is found in atherosclerotic plaques and because an increase in matrix metalloproteinase-9 (MMP-9) is strongly associated with plaque rupture, Singh et al. hypothesized that human CRP might promote oxLDL uptake and MMP-9 release in vivo in Wistar rats. Compared to serum albumin (huSA), CRP increased oxLDL uptake in the peritoneal and sterile pouch macrophages, increased intracellular cholesteryl ester accumulation, and increased MMP-9 activity in macrophages. It was also reported that human CRP increased MMP-9 activity by acting on nuclear factor-kB. Altogether, these results provide new pathophysiological roles for CRP and provide in vivo evidence supporting its direct involvement in atherosclerosis progression.
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