Colocalisation of intraplaque C reactive protein, complement, oxidised low density lipoprotein, and macrophages in stable and unstable angina and acute myocardial infarction.
BACKGROUND
C reactive protein (CRP), an important serum marker of atherosclerotic vascular disease, has recently been reported to be active inside human atherosclerotic plaques.


OBJECTIVE
To investigate the simultaneous presence of macrophages, CRP, membrane attack complex C5b-9 (MAC), and oxidised low density lipoprotein (oxLDL) in atherectomy specimens from patients with different coronary syndromes.


METHODS
In total, 54 patients with stable angina (SA; n = 21), unstable angina (UA; n = 15), and myocardial infarction (MI; n = 18) underwent directional coronary atherectomy for coronary lesions. Cryostat sections of atherosclerotic plaques were immunohistochemically stained with monoclonal antibodies: anti-CD68 (macrophages), anti-5G4 (CRP), aE11 (MAC), and 12E7 (oxLDL). Immunopositive areas were evaluated in relation to fibrous and neointima tissues, atheroma, and media. Quantitative analysis was performed using image cytometry with systematic random sampling (percentage immunopositive/total tissue area).


RESULTS
Macrophages, CRP, MAC, and oxLDL were simultaneously present in a higher proportion of fibrous tissue and atheroma of atherectomy specimens from patients with UA and MI compared with SA (p<0.05). Quantitative analysis showed significantly higher mean percentages of macrophages in plaques from patients with MI (44%) than UA (30%; p<0.01) and SA (20%; p<0.001). Significantly higher mean percentages of CRP were also seen in MI (25%) and UA (25%) compared with SA (12%; p<0.05).


CONCLUSIONS
The presence of CRP, complement, and oxLDL in a high proportion of plaque tissue from patients with unstable coronary artery disease implies that these surrogate markers have important proinflammatory effects inside atherosclerotic plaques. This may increase vulnerability to plaque rupture and thrombosis, with subsequent clinical sequelae.
Meuwissen
M
M
Department of Cardiology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. m.meuwissen@amc.uva.nl
van der Wal
A C
AC
Niessen
H W M
HW
Koch
K T
KT
de Winter
R J
RJ
van der Loos
C M
CM
Rittersma
S Z H
SZ
Chamuleau
S A J
SA
Tijssen
J G P
JG
Becker
A E
AE
Piek
J J
JJ
D000787:Angina Pectoris / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000789:Angina, Unstable / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D017225:Atherectomy, Coronary; D002097:C-Reactive Protein / Q000032:analysis*; D015938:Complement Membrane Attack Complex / Q000032:analysis*; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D008077:Lipoproteins, LDL / Q000032:analysis*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
D015938:Complement Membrane Attack Complex; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein