The focus of the Henke laboratory is to determine the basic mechanisms of deep vein thrombosis resolution as well as the effect of the vein wall. The clinical relevance of this is that DVT is a major, and until recently, neglected health problem. The acute sequlae may be pulmonary embolism which can be fatal and more commonly, post thrombotic syndrome with its significant morbidity. Using state of the art physiological, immunological and molecular biological techniques, mouse and rat models are used to define the process of venous thrombus resolution. Over the last 5 years, much has been learned. First, the thrombus is biologically active with leukocytes directing the adjacent vein wall response. Secondly, the thrombi undergo neovascularization as a normal process to allow return of prograde blood flow. Third, the leukocyte is essential for thrombus resolution, and is directed by a class of signaling molecules termed chemokines. More specifically, neutrophils are essential for early DVT resolution while monocytes are critical for the later processes. Forth, matrix metalloproteinases play an integral role in both vein wall injury and remodeling as well as DVT resolution. Our current National Institutes of Health R-01 grant specifically applies to this. Lastly, the mechanism of how a thrombus forms directs the vein wall response. For example, stasis derived DVT is more damaging to the vein wall than endothelial injury or an inert stretch injury. This latter data is clinically applicable because it suggests that methods to actively remove thrombus in a timely fashion, rather than passive anticoagulation, may decrease the long term risk of fibrotic injury.