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
