Circulating microparticles generate and transport monomeric C-reactive protein in patients with myocardial infarction.
OBJECTIVE
Elevated serum C-reactive protein (CRP) following myocardial infarction (MI) is associated with poor outcomes. Although animal studies have indicated a direct pathogenic role of CRP, the mechanism underlying this remains elusive. Dissociation of pentameric CRP (pCRP) into pro-inflammatory monomers (mCRP) may directly link CRP to inflammation. We investigated whether cellular microparticles (MPs) can convert pCRP to mCRP and transport mCRP following MI.


RESULTS
MPs enriched in lysophosphatidylcholine were obtained from cell cultures and patient whole-blood samples collected following acute MI and control groups. Samples were analysed by native western blotting and flow cytometry. MPs were loaded with mCRP in vitro and incubated with endothelial cells prior to staining with monoclonal antibodies. In vitro experiments demonstrated that MPs were capable of converting pCRP to mCRP which could be inhibited by the anti-CRP compound 1,6 bis-phosphocholine. Significantly more mCRP was detected on MPs from patients following MI compared with control groups by western blotting and flow cytometry (P = 0.0005 for association). MPs containing mCRP were able to bind to the surface of endothelial cells and generate pro-inflammatory signals in vitro, suggesting a possible role of MPs in transport and delivery of pro-inflammatory mCRP in vascular disease.


CONCLUSIONS
Circulating MPs can convert pCRP to pro-inflammatory mCRP in patients following MI, demonstrating for the first time mCRP generation in vivo and its detection in circulating blood. MPs can bind to cell membranes and transfer mCRP to the cell surface, suggesting a possible mCRP transport/delivery role of MPs in the circulation.
Atherothrombosis and Vascular Biology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia. jonathon.habersberger@bakeridi.edu.au
Jonathon
J
Habersberger
Frederik
F
Strang
Amelie
A
Scheichl
Nay
N
Htun
Nicole
N
Bassler
Ruusu-Maaria
RM
Merivirta
Philipp
P
Diehl
Guy
G
Krippner
Peter
P
Meikle
Steffen U
SU
Eisenhardt
Ian
I
Meredith
Karlheinz
K
Peter
D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000378:metabolism*; D002460:Cell Line; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*
D008246:Lysophospholipids; D002097:C-Reactive Protein