TY - JOUR
T1 - LECTIN PATHWAY OF COMPLEMENT ACTIVATION IS ASSOCIATED WITH VULNERABILITY OF ATHEROSCLEROTIC PLAQUES
AU - Fumagalli, Stefano
AU - Perego, Carlo
AU - Zangari, Rosalia
AU - De Blasio, Daiana
AU - Oggioni, Marco
AU - De Nigris, Francesca
AU - Snider, Francesco
AU - Garred, Peter
AU - Ferrante, Angela Maria Rosaria
AU - De Simoni, Maria-Grazia
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - ATHEROSCLEROSIS
KW - CARDIOVASCULAR DISEASES
KW - COMPLEMENT SYSTEM PROTEINS
KW - FICOLIN-2
KW - VULNERABLE PLAQUES
KW - ATHEROSCLEROSIS
KW - CARDIOVASCULAR DISEASES
KW - COMPLEMENT SYSTEM PROTEINS
KW - FICOLIN-2
KW - VULNERABLE PLAQUES
UR - http://hdl.handle.net/10807/97065
U2 - https://doi.org/10.3389/fimmu.2017.00288
DO - https://doi.org/10.3389/fimmu.2017.00288
M3 - Article
SN - 1664-3224
VL - 2017
SP - 1
EP - 15
JO - Frontiers in Immunology
JF - Frontiers in Immunology
ER -