Related Experiment Video
Updated: May 19, 2026
Synthesis of Monocyte-targeting Peptide Amphiphile Micelles for Imaging of Atherosclerosis
Published on: November 17, 2017
Pentameric CRP attenuates inflammatory effects of mmLDL by inhibiting mmLDL--monocyte interactions
Steffen U Eisenhardt1, Julia Starke, Jan R Thiele
1Baker IDI Heart & Diabetes Institute, Melbourne, Victoria 8008, Australia. steffen.eisenhardt@uniklinik-freiburg.de
Abstract:
Previous studies have reported that C-reactive protein (CRP) interacting with low-density lipoproteins (LDL) affects macrophage activation and LDL uptake. However, the physiological relevance of CRP-LDL interaction with circulating monocytes remains elusive. Moreover, recent studies have shown that CRP exists in two isoforms with partly opposing characteristics pentameric (pCRP) and monomeric CRP (mCRP). Here we investigated the effects of CRP interacting with minimally modified low-density lipoprotein (mmLDL) interaction in regard to events involved in formation of atherosclerotic plaque. We analyzed the effect of mmLDL on human monocytes and found a substantial increase in monocyte activation as evaluated by CD11b/CD18 expression and increased monocyte adhesion under static and under shear flow conditions to human endothelial cells. Monocyte adhesion and activation was attenuated by pCRP via the prevention of mmLDL binding to monocytes. These anti-inflammatory properties of pCRP were lost when it dissociates to the monomeric form. Our results elucidate the physiological relevance of the CRP-mmLDL interaction and furthermore confirm the importance of the previously described pCRP dissociation to mCRP as a localized inflammatory "activation" mechanism.
Insights
Pentameric C-reactive protein (pCRP) prevents inflammatory monocyte activation by minimally modified low-density lipoproteins (mmLDL). Monomeric CRP (mCRP) loses this protective effect, highlighting its role in localized inflammation during atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Immunology
- Biochemistry
Background:
- C-reactive protein (CRP) and low-density lipoproteins (LDL) interactions influence macrophage behavior.
- The role of CRP-LDL interactions with circulating monocytes in atherosclerosis is not fully understood.
- CRP exists in pentameric (pCRP) and monomeric (mCRP) forms with distinct functions.
Purpose of the Study:
- To investigate the impact of CRP interacting with minimally modified LDL (mmLDL) on monocyte activation and adhesion.
- To determine the differential effects of pCRP and mCRP in the context of mmLDL interaction.
- To elucidate the physiological relevance of CRP-mmLDL interactions in atherosclerotic plaque formation.
Main Methods:
- Human monocytes were analyzed for activation (CD11b/CD18 expression) and adhesion to endothelial cells under static and shear flow conditions.
- The effects of mmLDL alone and in combination with pCRP and mCRP on monocytes were assessed.
- mmLDL binding to monocytes was evaluated to understand the mechanism of pCRP's action.
Main Results:
- Minimally modified LDL (mmLDL) significantly increased human monocyte activation and adhesion to endothelial cells.
- Pentameric CRP (pCRP) attenuated monocyte activation and adhesion by inhibiting mmLDL binding to monocytes.
- These anti-inflammatory effects of pCRP were abolished upon its dissociation to the monomeric form (mCRP).
Conclusions:
- CRP-mmLDL interactions are physiologically relevant in the context of atherosclerosis.
- pCRP exhibits anti-inflammatory properties by preventing mmLDL-induced monocyte activation and adhesion.
- The dissociation of pCRP to mCRP represents a localized inflammatory activation mechanism, underscoring the importance of CRP's quaternary structure.
