Document Detail

Novel insights into the critical role of bradykinin and the kinin B2 receptor for vascular recruitment of circulating endothelial repair-promoting mononuclear cell subsets: alterations in patients with coronary disease.
MedLine Citation:
PMID:  23275384     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Endothelial injury is considered critical for progression of atherosclerosis and its complications in coronary artery disease (CAD). The endothelial-supportive effects of bradykinin have mainly been attributed to activation of the resident endothelium. Here we newly investigate the role of bradykinin and its B2 receptor for the recruitment and functional activation of circulating mononuclear cell subsets with endothelial-repair promoting capacity, such as CD34(+)CXCR4(+)cells, at sites of arterial injury.
METHODS AND RESULTS: Bradykinin-B2-receptor (B2R) blockade by icatibant substantially impaired recruitment of circulating CD34(+)CXCR4(+) mononuclear cells (expressing high levels of B2R) to endothelial cells in vitro and to injured arterial wall in vivo, whereas recruitment of CD14(hi) monocytes (expressing low levels of B2R) was unchanged. Moreover, the capacity of genetically B2R-deficient bone marrow cells to promote endothelial repair in vivo was markedly impaired as compared with wild-type bone marrow cells. B2R expression was reduced on CD34(+)CXCR4(+)mononuclear cells and endothelial repair-promoting early outgrowth cells, but not on CD14(hi)monocytes, from CAD patients as compared with healthy subjects. B2R stimulation induced CD18 activation in early outgrowth cells of healthy subjects, but not in early outgrowth cells of CAD patients. Adenoviral B2R overexpression enhanced in vivo vascular recruitment and rescued impaired endothelial repair capacity of early outgrowth cells from CAD patients.
CONCLUSIONS: We newly report that bradykinin/B2R signaling may promote endothelial repair after arterial injury by selective recruitment and functional activation of B2R-expressing circulating mononuclear cell subsets. In CAD patients, B2R downregulation on endothelial repair-promoting circulating mononuclear cells substantially impairs the bradykinin-dependent endothelial repair, representing a novel mechanism promoting endothelial injury in CAD patients.
Nicolle Kränkel; Kira Kuschnerus; Maja Müller; Timo Speer; Pavani Mocharla; Paolo Madeddu; Michael Bader; Thomas F Lüscher; Ulf Landmesser
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-30
Journal Detail:
Title:  Circulation     Volume:  127     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-05     Completed Date:  2013-06-20     Revised Date:  2014-05-04    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  594-603     Citation Subset:  AIM; IM    
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MeSH Terms
Antigens, CD14 / metabolism
Antigens, CD34 / metabolism
Bradykinin / physiology*
Case-Control Studies
Cell Adhesion / physiology
Cells, Cultured
Coronary Disease / pathology*,  physiopathology
Endothelium, Vascular / pathology*,  physiopathology
Leukocytes, Mononuclear / immunology,  pathology*,  physiology
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Models, Animal
Receptor, Bradykinin B2 / deficiency,  genetics,  physiology*
Receptors, CXCR4 / metabolism
Signal Transduction / physiology*
Grant Support
G0900912//Medical Research Council
Reg. No./Substance:
0/Antigens, CD14; 0/Antigens, CD34; 0/Receptor, Bradykinin B2; 0/Receptors, CXCR4; S8TIM42R2W/Bradykinin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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