Stefano Fumagalli, Carlo Perego, Rosalia Zangari, Daiana De Blasio, Marco Oggioni, Francesca De Nigris, Francesco Snider, Peter Garred, Angela M. R. Ferrante, Maria-Grazia De Simoni
Abstract
Inflammatory mechanisms may be involved in atherosclerotic plaque rupture. By using a novel histology-based method to quantify plaque instability here, we assess whether lectin pathway (LP) of complement activation, a major inflammation arm, could represent an index of plaque instability. 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 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. 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. 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.
Pharmacology, Toxicology and Pharmaceutical Science
1
3%
Other
1
3%
Unknown
11
32%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 April 2017.
All research outputs
#15,394,133
of 26,311,549 outputs
Outputs from Frontiers in immunology
#13,540
of 32,936 outputs
Outputs of similar age
#168,528
of 326,766 outputs
Outputs of similar age from Frontiers in immunology
#247
of 444 outputs
Altmetric has tracked 26,311,549 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
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