Ficolin-2 serum levels predict the occurrence of acute coronary syndrome in patients with severe carotid artery stenosis. (April 2021)

• Record Type: Journal Article
• Authors: Carbone, Federico; Valente, Alessia; Perego, Carlo; Bertolotto, Maria; Pane, Bianca; Spinella, Giovanni; Palombo, Domenico; De Simoni, Maria-Grazia; Montecucco, Fabrizio; Fumagalli, Stefano
• Is Part Of: Pharmacological research. Volume 166(2021)
• Publication Date: 2021-04
• Subjects: ACE-I angiotensin converting enzyme inhibitor -- ARBs angiotensin receptor blockers -- BP blood pressure -- CAD coronary artery disease -- CCL C-C motif chemokine ligand -- CC cholesterol crystals -- CD cluster of differentiation -- ch cholesterol -- CI interval of confidence -- CV cardiovascular -- EDTA ethylenediaminetetraacetic acid -- HDL high-density lipoprotein -- HR hazard ratio -- ICAM intracellular adhesion molecule -- IGF insulin-like growth factor -- LDL low-density lipoprotein -- LP lectin pathway -- MACE major-adverse cardiovascular event -- MASP MBL-associated serine protease -- MBL mannose-binding lectin -- MMP matrix metalloprotease -- MPO myeloperoxidase -- NE neutrophil elastase -- NGS normal goat serum -- OPN osteopontin -- PCSK9 proprotein convertase subtilisin/kexin type 9 -- PMNs neutrophils -- RAAS renin-angiotensin-aldosterone system -- SMCs smooth muscle cells -- TAG triglyceride -- TIMP tissue inhibitor of metalloprotease -- total-c total cholesterol -- VCAM vascular cell adhesion molecule -- WBC white blood cells; Atherosclerosis -- Complement system -- Biomarkers -- Plaque vulnerability; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105462
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Background and purpose: erosion of vulnerable atherosclerotic plaques may cause life-threatening thromboembolic complications. There is indeed an urgent need to recognize a clear-cut biomarker able to identify vulnerable plaques. Here, we focused on circulating proteins belonging to the lectin pathway (LP) of complement activation. Methods: we analyzed mannose-binding lectin (MBL), ficolin-1, -2 and -3 (LP initiators) levels by ELISA in sera from n = 240 of an already published cohort of patients undergoing endarterectomy for severe carotid stenosis and followed-up until 18 months after surgery. Immunofluorescence followed by confocal and polarized light microscopy was used to detect LP initiator intraplaque localization. Spearman's rank test was drawn to investigate correlation between serum LP levels and circulating inflammatory proteins or intraplaque components. Survival analyses were then performed to test the predictive role of LP on long-term adverse outcome. Results: ficolins, but not MBL, correlated positively with 1) high circulating levels of inflammatory markers, including MPO, MMP-8, MMP-9, ICAM-1, osteopontin, neutrophil elastase, and; 2) immune cell intraplaque recruitment. Immunofluorescence showed ficolins in calcified plaques and ficolin-2 in cholesterol-enriched plaque regions in association with macrophages. In the multivariate survival analysis, ficolin-2 serum levels predicted a major adverse cardiovascular event during the follow-up, independently of symptomatic status and inflammatory markers (hazard ratio 38.6 [95 % CI 3.9–385.2]). Conclusions: ficolins support intraplaque immune cell recruitment and inflammatory processes ultimately leading to plaque vulnerability. Especially for ficolin-2 a strong predictive value toward adverse cardiovascular events was demonstrated. This evidence offers potentially new pharmacological target to dampen the inflammatory mechanisms leading to plaque vulnerability.