Document Detail

Expansion of necrotic core and shedding of Mertk receptor in human carotid plaques: a role for oxidized polyunsaturated fatty acids?
MedLine Citation:
PMID:  22997156     Owner:  NLM     Status:  Publisher    
AIM: Expansion of necrotic core (NC), a major feature responsible for plaque disruption, is likely the consequence of accelerated macrophage apoptosis coupled with defective phagocytic clearance (efferocytosis). The cleavage of the extracellular domain of Mer tyrosine kinase (Mertk) by metallopeptidase domain17 (Adam17) has been shown to produce a soluble Mertk protein (sMer), which can inhibit efferocytosis. Herein we analyzed the expression and localization of Mertk and Adam17 in the tissue around the necrotic core (TANC) and in the periphery (P) of human carotid plaques. Then we studied the mechanisms of NC expansion by evaluating which components of TANC induce Adam17 and the related cleavage of the extracellular domain of Mertk.Methods and ResultsWe studied 97 human carotid plaques. The expression of Mertk and Adam17 was found to be higher in TANC than in P (p<0.001). By immunohistochemistry Mertk was higher than Adam17 in the area of TANC near to the lumen (p<0.01) but much lower in the area close to NC (p<0.01). The extract of this portion of TANC increased the expression (mRNA) of Adam17 and Mertk (p<0.01) in macrophage-like THP-1 cells but it also induced the cleavage of the extracellular domain of Mertk generating sMer in the medium (p<0.01). This effect of TANC extract was most evoked by its content in F(2)-isoprostanes, hydroxyoctadecadienoic acids and hydroxytetraenoic acids. CONCLUSIONS: Some oxidized derivatives of polyunsaturated fatty acids contained in TANC of human carotid plaques are strong inducers of Adam17, which in turn leads to the generation of sMer, which can inhibit efferocytosis.
Ulisse Garbin; Elda Baggio; Chiara Stranieri; Andrea Pasini; Stefania Manfro; Chiara Mozzini; Paola Vallerio; Giovanni Lipari; Flavia Merigo; Giancesare Guidi; Luciano Cominacini; Anna Fratta Pasini
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-20
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Medicine, University of Verona, Verona, Italy.
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