LECTIN PATHWAY OF COMPLEMENT ACTIVATION IS ASSOCIATED WITH VULNERABILITY OF ATHEROSCLEROTIC PLAQUES

S Fumagalli, C Perego, R Zangari, D De Blasio, M Oggioni, F De Nigris, F Snider, P Garred, Angela Maria Rosaria Ferrante, MG De Simoni

Risultato della ricerca: Contributo in rivistaArticolo

17 Citazioni (Scopus)

Abstract

Inflammatory mechanisms may be involved in atherosclerotic plaque rupture. By using\r\na novel histology-based method to quantify plaque instability here, we assess whether\r\nlectin pathway (LP) of complement activation, a major inflammation arm, could represent\r\nan index of plaque instability. Plaques from 42 consecutive patients undergoing carotid\r\nendarterectomy were stained with hematoxylin-eosin and the lipid core, cholesterol\r\nclefts, hemorrhagic content, thickness of tunica media, and intima, including or not\r\ninfiltration of cellular debris and cholesterol, were determined. The presence of ficolin-1,\r\n-2, and -3 and mannose-binding lectin (MBL), LP initiators, was assessed in the plaques\r\nby immunofluorescence and in plasma by ELISA. LP activation was assessed in plasma\r\nby functional in vitro assays. Patients presenting low stenosis (≤75%) had higher hemorrhagic\r\ncontent than those with high stenosis (>75%), indicating increased erosion.\r\nIncreased hemorrhagic content and tunica media thickness, as well as decreased lipid\r\ncore and infiltrated content were associated with vulnerable plaques and therefore used\r\nto establish a plaque vulnerability score that allowed to classify patients according to\r\nplaque vulnerability. Ficolins and MBL were found both in plaques’ necrotic core and\r\ntunica media. Patients with vulnerable plaques showed decreased plasma levels and\r\nintraplaque deposition of ficolin-2. Symptomatic patients experiencing a transient ischemic\r\nattack had lower plasma levels of ficolin-1. We show that the LP initiators are\r\npresent within the plaques and their circulating levels change in atherosclerotic patients.\r\nIn particular, we show that decreased ficolin-2 levels are associated with rupture-prone\r\nvulnerable plaques, indicating its potential use as marker for cardiovascular risk assessment\r\nin atherosclerotic patients.
Lingua originaleInglese
pagine (da-a)1-15
Numero di pagine15
RivistaFrontiers in Immunology
Volume2017
Numero di pubblicazione8
DOI
Stato di pubblicazionePubblicato - 2017
Pubblicato esternamente

All Science Journal Classification (ASJC) codes

  • Immunologia e Allergia
  • Immunologia

Keywords

  • ATHEROSCLEROSIS
  • CARDIOVASCULAR DISEASES
  • COMPLEMENT SYSTEM PROTEINS
  • FICOLIN-2
  • VULNERABLE PLAQUES

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