Background: Inflammatory mechanisms may be involved in
atherosclerotic plaque rupture. By using a novel histology-based
method to quantify plaque instability here we assess whether the
activation of the lectin complement pathway (LP), a major inflammation
arm, could represent an index of plaque instability.
Materials and methods: Plaques from 42 consecutive
patients undergoing carotid endarterectomy were stained with
hematoxylin-eosin and the lipid core, cholesterol clefts, hemorrhagic
content, thickness of tunica media and intima, including or
not infiltration of cellular debris and cholesterol, were determined.
The occurrence of fibrous cap rupture indicating a vulnerable
eroded plaque was also assessed. The presence of ficolin-1, -2 and
-3 and mannose-binding lectin (MBL), LP initiators, was assessed
in the plaques by immunofluorescence and in plasma by ELISA. LP
activation was assessed in plasma by functional in vitro assays.
Results and conclusions: Patients presenting low stenosis
(≤75%) had higher hemorrhagic content than those with high
stenosis (>75%), indicating increased erosion. Increased hemorrhagic
content and tunica media thickness, as well as decreased
lipid core and infiltrated content were associated with vulnerable
plaques and therefore used to establish a plaque vulnerability
score that allowed to classify patients according to plaque vulnerability.
Ficolins and MBL were found both in plaques’ necrotic
core and tunica media. Patients with vulnerable plaques showed
decreased plasma levels and intraplaque deposition of ficolin-2.
Symptomatic patients experiencing a transient ischemic attack had
lower plasma levels of ficolin-1. In conclusion, we show that the
LP initiators are present within the plaques and their circulating
levels change in atherosclerotic patients. In particular we show
that decreased ficolin-2 levels are associated with rupture-prone
vulnerable plaques, indicating its potential use as marker for cardiovascular
risk assessment in atherosclerotic patients.
- Complement activation
- Immunology and Allergy