ORIGINAL ARTICLE

Colocalisation of intraplaque C reactive protein, complement, oxidised low density lipoprotein, and macrophages in stable and unstable angina and acute myocardial infarction

M Meuwissen¹, A C van der Wal², H W M Niessen³, K T Koch¹, R J de Winter¹, C M van der Loos², S Z H Rittersma¹, S A J Chamuleau¹, J G P Tijssen¹, A E Becker², J J Piek¹

¹ Department of Cardiology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
² Department of Cardiovascular Pathology, Academic Medical Centre, University of Amsterdam
³ Department of Pathology, Vrije Universiteit Medical Centre, Amsterdam, 1081 HV, The Netherlands

Correspondence to:
Correspondence to:
Dr J J Piek
Academic Medical Centre, Department of Cardiology, University of Amsterdam, Room B2-250, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; m.meuwissen{at}amc.uva.nl

Background: C reactive protein (CRP), an important serum marker of atherosclerotic vascular disease, has recently been reported to be active inside human atherosclerotic plaques.

Aims: 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.

Abbreviations: CRP, C reactive protein; MAC, membrane attack complex; MI, myocardial infarction; oxLDL, oxidised low density lipoprotein; SA, stable angina; UA, unstable angina

Keywords: acute coronary syndromes; atherosclerosis; plaque inflammation; C reactive protein

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