Intracoronary platelet and monocyte activation status within platelet-monocyte complexes are determinants of inflammation in ST elevation myocardial infarction¹

Article type: Research Article

Authors: Majumder, B.^a | Koganti, S.^a | Lowdell, M.W.^b | Rakhit, R.D.^{a; *}

Affiliations: [a] Department of Cardiology, Royal Free Hospital, London, UK | [b] Department of Haematology, Royal Free Hospital, London, UK

Correspondence: [*] Corresponding author: Roby Rakhit, Department of Cardiology, Royal Free Hospital, London, NW3 2QG, UK. Tel.: +44 2077940500; E-mail: roby.rakhit@nhs.net.

Note: [1] Work was carried out at the Royal Free Hospital, Pond street, London, NW3 2QG.

Abstract: INTRODUCTION: Platelet Monocyte Complexes (PMCs) are commonly expressed in coronary artery disease but their pathologic significance in ST elevation myocardial infarction (STEMI) is unclear. This study evaluates the relationship between locally activated PMCs and intracoronary inflammation in stable and unstable coronary disease. MATERIAL AND METHODS: Micro catheter aspirated blood samples of 15 STEMI and 7 stable angina patients are collected from the coronary artery (CA), aorta (AO) and right atrium (RA). Samples are labelled with monoclonal antibodies and prepared for flow cytometry. CD 14 and CD 61 double positive cells are identified as PMC. P-selectin expression is identified by additional CD62P positivity and TF expression by additional CD142 positivity. Plasma TNF-alpha and IL-6 are measured using ELISA and CRP is measured in plasma using a high sensitivity automated microparticle enhanced latex turbidimetric immunoassay. RESULTS: No site-specific difference is seen in overall PMC expression in STEMI or stable angina. Surface P-selectin expression in STEMI [median (IQR)] is significantly higher in CA [35.01 (23.15–56.99)] compared with AO [15.99 (10.3–18.85)] or RA [14.02 (10.42–26.08)] (p = 0.003). Intracoronary PMC correlates significantly with intracoronary TNF-alpha (r = 0.87, p = 0.001) and intracoronary IL-6 (r = 0.76, p = 0.03). Bound monocytes within P-selectin positive and tissue factor positive complexes correlate positively with intracoronary TNF-alpha (r = 0.81, p = 0.008 & r = 0.80, p = 0.009 respectively) and IL-6 (r = 0.54, p = 0.16 & r = 0.71, p = 0.05 respectively). No such correlation is observed in the peripheral circulation of STEMI and stable angina patients. CONCLUSION: Inflammation is not attributable to PMC formation per se. However, increased intracoronary P-selectin expression by activated platelets and tissue factor expression by activated monocytes within the complexes are determinants of local intracoronary inflammatory burden in STEMI.

Keywords: Platelet monocyte complex, platelet and monocyte activation status, intracoronary inflammation, ST elevation myocardial infarction

DOI: 10.3233/CH-162040

Journal: Clinical Hemorheology and Microcirculation, vol. 64, no. 1, pp. 35-46, 2016