Author:
Macarie Răzvan Daniel,Tucureanu Monica Mădălina,Ciortan Letiția,Gan Ana-Maria,Butoi Elena,Mânduțeanu Ileana
Abstract
AbstractFicolin-2, recently identified in atherosclerotic plaques, has been correlated with future acute cardiovascular events, but its role remains unknown. We hypothesize that it could influence plaque vulnerability by interfering in the cross-talk between macrophages (MØ) and smooth muscle cells (SMC). To examine its role and mechanism of action, we exposed an in-vitro co-culture system of SMC and MØ to ficolin-2 (10 µg/mL) and then performed cytokine array, protease array, ELISA, qPCR, Western Blot, and monocyte transmigration assay. Carotid plaque samples from atherosclerotic patients with high plasma levels of ficolin-2 were analyzed by immunofluorescence. We show that ficolin-2: (i) promotes a pro-inflammatory phenotype in SMC following interaction with MØ by elevating the gene expression of MCP-1, upregulating gene and protein expression of IL-6 and TLR4, and by activating ERK/MAPK and NF-KB signaling pathways; (ii) increased IL-1β, IL-6, and MIP-1β in MØ beyond the level induced by cellular interaction with SMC; (iii) elevated the secretion of IL-1β, IL-6, and CCL4 in the conditioned medium; (iv) enhanced monocyte transmigration and (v) in atherosclerotic plaques from patients with high plasma levels of ficolin-2, we observed co-localization of ficolin-2 with SMC marker αSMA and the cytokines IL-1β and IL-6. These findings shed light on previously unknown mechanisms underlying ficolin-2–dependent pathological inflammation in atherosclerotic plaques.
Funder
Romanian Academy
Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii
ERANET NEURON JTC 2019
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
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