Deletion of cysteine-cysteine receptor 7 promotes fibrotic injury in experimental post-thrombotic vein wall remodeling.
Arterioscler Thromb Vasc Biol
; 34(2): 377-85, 2014 Feb.
Article
in En
| MEDLINE
| ID: mdl-24311382
ABSTRACT
OBJECTIVE:
Deep vein thrombosis (VT) can result in vein wall injury, which clinically manifests as post-thrombotic syndrome. Postinjury fibrosis may be modulated in part through cellular cysteine-cysteine receptor 7 (CCR7)-mediated events. We tested the hypothesis that late vein wall fibrotic remodeling is dependent on CCR7. APPROACH ANDRESULTS:
CCR7(-/-) and C57BL/6 wild-type mice had inferior vena cava VT induced by nonstasis or stasis mechanisms. In both models, VT size was largest at day 1 and trended down by day 21, and CCR7(+) cells peaked at day 8 in wild-type mice. No significant differences in VT resolution were found in CCR7(-/-) as compared with wild type in either model. In the nonstasis VT model, vein wall changes consistent with fibrotic injury were evidenced by significant increases in collagen I, III, matrix metalloproteinase 2, and transforming growth factor-ß gene expression, increases in α-smooth muscle actin and fibroblast specific protein-1 antigen, and total collagen at 8 days. Correspondingly, SM22α and fibroblast specific protein-1, but not DDR2(+) cells, were increased at 8 days. Early wild-type thrombus exposure inhibited profibrotic gene expression in CCR7(-/-) in ex vivo vein wall culture. Bone marrow chimera experiments further showed that circulating CCR7(+) leukocytes partially rescued midterm profibrotic changes in CCR7(-/-) mice. In human histological sections of chronic thrombosed femoral veins, CCR7(+) cells were present in the fibrotic areas.CONCLUSIONS:
Post-thrombotic vein wall remodeling is impaired in CCR7(-/-) mice, with a profibrotic phenotype, is dependent on the thrombotic mechanism, and is mediated by circulating CCR7(+) cells. Unlike other postinjury fibrotic responses, CCR7(+) signaling may be important for positive vein wall remodeling after VT.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Vena Cava, Inferior
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Venous Thrombosis
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Postthrombotic Syndrome
/
Receptors, CCR7
Type of study:
Prognostic_studies
Limits:
Animals
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Humans
/
Male
Language:
En
Journal:
Arterioscler Thromb Vasc Biol
Journal subject:
ANGIOLOGIA
Year:
2014
Type:
Article