title: Lectin Pathway of Complement Activation Is Associated with Vulnerability of Atherosclerotic Plaques.
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 functionalin vitroassays. 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.
authors.affiliation: Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fumagalli
authors.affiliation: Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Perego
authors.affiliation: Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Zangari
authors.affiliation: Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: Daiana
authors.initials: D
authors.lastname: De Blasio
authors.affiliation: Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Oggioni
authors.affiliation: Vascular Surgery Unit, Catholic University of Sacred Heart Medical School "A. Gemelli University Hospital" Foundation , Rome , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Nigris
authors.affiliation: Vascular Surgery Unit, Catholic University of Sacred Heart Medical School "A. Gemelli University Hospital" Foundation , Rome , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Snider
authors.affiliation: Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Faculty of Medical and Health Sciences, University of Copenhagen , Copenhagen , Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.affiliation: Vascular Surgery Unit, Catholic University of Sacred Heart Medical School "A. Gemelli University Hospital" Foundation , Rome , Italy.
authors.forename: Angela M R
authors.initials: AM
authors.lastname: Ferrante
authors.affiliation: Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri , Milan , Italy.
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: De Simoni
keywords: atherosclerosis; cardiovascular diseases; complement system proteins; ficolin-2; vulnerable plaques