Pre-Clinical Model to Study Recurrent Venous Thrombosis in the Inferior Vena Cava.
Thromb Haemost
; 118(6): 1048-1057, 2018 06.
Article
em En
| MEDLINE
| ID: mdl-29695021
ABSTRACT
BACKGROUND:
Patients undergoing deep vein thrombosis (VT) have over 30% recurrence, directly increasing their risk of post-thrombotic syndrome. Current murine models of inferior vena cava (IVC) VT model host one thrombosis event.OBJECTIVE:
We aimed to develop a murine model to study IVC recurrent VT in mice. MATERIALS ANDMETHODS:
An initial VT was induced using the electrolytic IVC model (EIM) with constant blood flow. This approach takes advantage of the restored vein lumen 21 days after a single VT event in the EIM demonstrated by ultrasound. We then induced a second VT 21 days later, using either EIM or an IVC ligation model for comparison. The control groups were a sham surgery and, 21 days later, either EIM or IVC ligation. IVC wall and thrombus were harvested 2 days after the second insult and analysed for IVC and thrombus size, gene expression of fibrotic markers, histology for collagen and Western blot for citrullinated histone 3 (Cit-H3) and fibrin.RESULTS:
Ultrasound confirmed the first VT and its progressive resolution with an anatomical channel allowing room for the second thrombus by day 21. As compared with a primary VT, recurrent VT has heavier walls with significant up-regulation of transforming growth factor-ß (TGF-ß), elastin, interleukin (IL)-6, matrix metallopeptidase 9 (MMP9), MMP2 and a thrombus with high citrullinated histone-3 and fibrin content.CONCLUSION:
Experimental recurrent thrombi are structurally and compositionally different from the primary VT, with a greater pro-fibrotic remodelling vein wall profile. This work provides a VT recurrence IVC model that will help to improve the current understanding of the biological mechanisms and directed treatment of recurrent VT.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Veia Cava Inferior
/
Trombose Venosa
/
Modelos Animais de Doenças
/
Síndrome Pós-Trombótica
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Thromb Haemost
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos