Antiproliferative agent attenuates postthrombotic vein wall remodeling in murine and human subjects

Abstract

BackgroundDespite appropriate treatment, up to 50% of patients with proximal deep vein thrombosis will develop postthrombotic syndrome (PTS). Once PTS occurs, there is no specific treatment, and some patients constantly experience intolerable symptoms. Hence, prevention of PTS is important. ObjectivesTo characterize vein wall remodeling after thrombus and investigate the effects of antiproliferative agent on postthrombotic vein wall remodeling in murine and human subjects. MethodsFeatures of postthrombotic vein wall remodeling in murine and human subjects were characterized using imaging and histologic examinations. Paclitaxel-loaded hydrogels were used to assess the effects of antiproliferative agent on the remodeling in murine model. Based on the abovementioned results, a pilot study was conducted to assess the effects of paclitaxel-coated balloon dilation in patients with severe PTS experiencing intolerable symptoms. The control cohort was obtained by 1:1 propensity score matching from a prospective database. ResultsStructural and functional alterations in postthrombotic vein wall were verified by imaging and histologic examinations, and predominant active α-smooth muscle actin–positive cells and fibroblast-specific protein 1–positive cells proliferation was observed. In the murine model, the application of paclitaxel-loaded hydrogels inhibited the remodeling. In the pilot clinical study, patients receiving drug-coated balloon demonstrated benefits in Villalta scores and venous clinical severity scores compared with those not receiving drug-coated balloon, and no severe adverse events were reported except for thrombosis recurrence. ConclusionCell proliferation plays an important role in postthrombotic vein wall remodeling. Inhibition of cell proliferation inhibits the remodeling in murine model and may reduce signs and symptoms in patients with severe PTS.