Human C-reactive protein promotes oxidized low density lipoprotein uptake and matrix metalloproteinase-9 release in wistar rats

U. Singh, M. R. Dasu, P. G. Yancey, Alaa M Afify, S. Devaraj, I. Jialal

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

C-reactive protein (CRP) is present in the atherosclerotic plaques and appears to promote atherogenesis. Intraplaque CRP colocalizes with oxidized low density lipoprotein (OxLDL) and macrophages in human atherosclerotic lesions. Matrix metalloproteinase-9 (MMP-9) has been implicated in plaque rupture. CRP promotes OxLDL uptake and MMP induction in vitro; however, these have not been investigated in vivo. We examined the effect of CRP on OxLDL uptake and MMP-9 production in vivo in Wistar rats. CRP significantly increased OxLDL uptake in the peritoneal and sterile pouch macrophages compared with human serum albumin (huSA). CRP also significantly increased intracellular cholesteryl ester accumulation compared with huSA. The increased uptake of OxLDL by CRP was inhibited by pretreatment with antibodies to CD32, CD64, CD36, and fucoidin, suggesting uptake by both scavenger receptors and Fc-γ receptors. Furthermore, CRP treatment increased MMP-9 activity in macrophages compared with huSA, which was abrogated by inhibitors to p38 mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), and nuclear factor (NF)-κB but not Jun N-terminal kinase ( JNK) before human CRP treat- ment. Because OxLDL uptake by macrophages contributes to foam cell formation and MMP release contributes to plaque instability, this study provides novel in vivo evidence for the role of CRP in atherosclerosis.

Original languageEnglish (US)
Pages (from-to)1015-1023
Number of pages9
JournalJournal of Lipid Research
Volume49
Issue number5
DOIs
StatePublished - May 1 2008

Keywords

  • Macrophages sterile pouch
  • Mechanistic insights

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

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