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 AND RESULTS: 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.
Subject(s)
Postthrombotic Syndrome/metabolism , Receptors, CCR7/deficiency , Receptors, CCR7/metabolism , Vena Cava, Inferior/metabolism , Venous Thrombosis/metabolism , Animals , Bone Marrow Transplantation , Collagen Type I/metabolism , Collagen Type III/metabolism , Disease Models, Animal , Fibrosis , Genotype , Humans , Male , Matrix Metalloproteinase 2/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Microfilament Proteins/metabolism , Muscle Proteins/metabolism , Phenotype , Postthrombotic Syndrome/genetics , Postthrombotic Syndrome/pathology , Receptors, CCR7/genetics , Time Factors , Tissue Culture Techniques , Transforming Growth Factor beta/metabolism , Vena Cava, Inferior/pathology , Venous Thrombosis/genetics , Venous Thrombosis/pathologyABSTRACT
INTRODUCTION: Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of patients with underlying sever aortic valve stenosis across all spectrum of the disease. CT imaging is so crucial to the pre procedural planning, to incorporate the information from the CT imaging in the decision making intraprocedurally and to predict and identity the post procedural complications.Areas covered: In this article, we review available studies on CT role in TAVR procedure and provide update on the technological developments and clinical applications.Expert opinion: CT imaging, with its high resolution, and in particular its utilization in aortic annular measurements, bicuspid aortic valve assessment, hypoattenuated leaflet thickening and valve in valve therapy proved to be the ideal approach to study the mechanisms of aortic stenosis, detection of high-risk anatomy, more accurate risk stratification and thus to allow a personalized catheter based intervention of the affected patients.