Deletion of Cysteine-Cysteine Receptor 7 Promotes Fibrotic Injury in Experimental Post-Thrombotic Vein Wall Remodeling

• DOI: 10.1161/atvbaha.113.302428
• Publication Date: 2013-12-06T04:59:10Z
• Authors: Adriana Laser; Megan Elfline; Cathy Luke; Dallas Slack; Anuj Shah; Vikram Sood; Barry Deatrick; Brendan McEvoy; Carson Ostra; Anthony Comerota; Steven Kunkel; Cory Hogaboam; Peter K. Henke
• Keywords: Male; Mice, Knockout; Receptors, CCR7; Time Factors; Genotype; Microfilament Proteins; Muscle Proteins; Fibrosis; Collagen Type I; Postthrombotic Syndrome; Mice, Inbred C57BL; Tissue Culture Techniques; Disease Models, Animal; Mice; 03 medical and health sciences; Collagen Type III; Phenotype; 0302 clinical medicine; Animals; Humans; Matrix Metalloproteinase 2; Bone Marrow Transplantation

Deep vein thrombosis (VT) can result in wall injury, which clinically manifests as post-thrombotic syndrome. Postinjury fibrosis may be modulated part through cellular cysteine-cysteine receptor 7 (CCR7)-mediated events. We tested the hypothesis that late fibrotic remodeling is dependent on CCR7.CCR7(-/-) and C57BL/6 wild-type mice had inferior vena cava VT induced by nonstasis or stasis mechanisms. In both models, size was largest at day 1 trended down 21, CCR7(+) cells peaked 8 mice. No significant differences resolution were found CCR7(-/-) compared with wild type either model. model, changes consistent injury evidenced increases collagen I, III, matrix metalloproteinase 2, transforming growth factor-β gene expression, α-smooth muscle actin fibroblast specific protein-1 antigen, total days. Correspondingly, SM22α protein-1, but not DDR2(+) cells, increased Early thrombus exposure inhibited profibrotic expression ex vivo culture. Bone marrow chimera experiments further showed circulating leukocytes partially rescued midterm human histological sections of chronic thrombosed femoral veins, present areas.Post-thrombotic impaired mice, a phenotype, thrombotic mechanism, mediated cells. Unlike other postinjury responses, signaling important for positive after VT.