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Thromb Haemost 2018; 118(06): 1078-1087
DOI: 10.1055/s-0038-1641749
Atherosclerosis and Ischaemic Disease
Schattauer GmbH Stuttgart

Neutrophil Extracellular Traps Participate in All Different Types of Thrombotic and Haemorrhagic Complications of Coronary Atherosclerosis

Kartika R. Pertiwi
1   Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
2   Department of Biology Education, Yogyakarta State University, Yogyakarta, Indonesia
,
Allard C. van der Wal
1   Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
,
Dara R. Pabittei
3   Department of Cardiothoracic Surgery, Academic Medical Center, Amsterdam, The Netherlands
,
Claire Mackaaij
1   Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
,
Marinus B. van Leeuwen
4   Precision and Decentralized Diagnostics, Philips Research, Eindhoven, The Netherlands
,
Xiaofei Li
1   Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
,
Onno J. de Boer
1   Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
› Author Affiliations Funding This study was supported by the PhD Fellowship Grant for Kartika R. Pertiwi from Indonesian Endowment Fund for Education (LPDP).
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Publication History

20 September 2017

06 March 2018

Publication Date:
19 April 2018 (online)

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Abstract

Acute coronary syndromes can be initiated by either atherosclerotic fibrous cap ruptures, superficial plaque erosions or intraplaque haemorrhages (IPHs). Since neutrophil extracellular traps (NETs) display pro-inflammatory and pro-thrombotic properties, we investigated the presence, extent and distribution of neutrophils and NETs in different types of plaque complications in relation to the age of overlying thrombus mass or haemorrhage. Sixty-four paraffin-embedded coronary plaque segments of 30 acute myocardial infarction patients were retrieved from the autopsy archives, which contained 44 complicated plaques (17 IPHs, 9 erosions and 18 ruptures) and 20 intact plaques. Complicated plaques were further categorized according to the histological age of thrombus or haemorrhage. Immunohistochemistry was performed to visualize neutrophils (anti-myeloperoxidase, anti-elastase and anti-CD177) and NETs (anti-citrullinated histone-3 and anti-peptidyl-arginine-deiminase-4). The results were scored semi-quantitatively. Neutrophils and NETs were abundantly present in all types of complicated, but not in intact, plaques (p < 0.05). They were found in thrombus, haemorrhages and at the thrombus–plaque interface, with no significant differences in extent between ruptures, erosions and IPHs. Interestingly, adjacent perivascular tissue of complicated, but not of intact plaques, also contained high numbers of neutrophils and NETs (p < 0.05). In thrombus and haemorrhage of different age, neutrophils and NETs were more frequently present in non-organized (fresh) thrombi and in on-going IPHs. In conclusion, netosis is a prominent pro-thrombotic participant in all distinct types of atherothrombosis, which may facilitate the progression of thrombotic or haemorrhagic complications and thus the onset of ensuing clinical coronary ischemic syndromes.

Keywords

atherosclerosis - acute myocardial infarction - neutrophil extracellular traps - plaque complication - thrombosis

Supplementary Material

 

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