Deep vein thrombosis resolution is not accelerated with increased neovascularization

Abstract

Pro-angiogenic compounds increase thrombus neovascularization, but this does not correlate with smaller or less fibrotic DVT. Mechanisms other than neovascularization may be more important to hasten DVT dissolution. Clinical relevance Improved therapy for deep venous thrombosis (DVT) will ideally increase the rate of thrombus dissolution and eliminate the bleeding risks of anticoagulation. This study evaluated promoting DVT neovascularization with angiogenic chemokines, and, while successful by experimental measures, this did not translate into smaller DVT. Solely promoting thrombus neovascularization will not likely speed resolution.

Induction of Heme Oxygenase-1 is a Beneficial Response in a Murine Model of Venous Thrombosis

“…We measured clot size at day 2 and day 10 following ligation of the IVC in HO-1 ϩ/ϩ and HO-1 Ϫ/Ϫ mice, as clot size is widely regarded and used as a valid determinant of clot resolution in this model of venous thrombosis. [21][22][23]32 As demonstrated in Figure 4, clot size, as measured by clot weight and clot length, was virtually identical at day 2 after ligation of the IVC in HO-1 ϩ/ϩ and HO-1 Ϫ/Ϫ mice. However, at day 10, the clot size was markedly greater in the HO-1 Ϫ/Ϫ mice as compared to the HO-1 ϩ/ϩ mice as determined by the weight and length of the clot ( Figure 4), and the weight/length ratio of the clot ( Figure 5A).…”

Targeted Deletion of CCR2 Impairs Deep Vein Thombosis Resolution in a Mouse Model

“…The Lisca laser doppler (Lisca) was used to assess in vivo microvascular IVC blood flow, based on techniques described (33). After laparotomy, the pre-IVC ligation, immediate postligation, and harvest blood flow through the exposed IVC region of interest was assessed; a 5-s scan with 30-s interval, over four scanning cycles, was performed.…”

“…Laser doppler imaging detects blood flow within and around the thrombosed IVC (33). In WT controls, blood flow returns to nearly 70% of normal nonthrombosed IVC flow by 21 days.…”

“…Thrombus mediators are produced both in the thrombus and by the surrounding vein wall cells, given the intimate physical proximity of the thrombus-vein wall interface (5,18,33). To evaluate the thrombus milieu, only the thrombus (and not wall) was evaluated at 2, 4, and 8 days after DVT (for which complete thrombus extraction is possible) for analysis (Fig.…”

Plasmin Inhibition Increases MMP-9 Activity and Decreases Vein Wall Stiffness During Venous Thrombosis Resolution

“…Stasis thrombosis was induced by IVC ligation as described. 29,30 Briefly, a laparotomy with ligation of the IVC below the renal veins and all visible side branches was performed. Rats were injected with Trasylol® (2.8 mg/kg AP; Bayer Pharmaceuticals Corporation, West Haven, CT) or control saline via tail vein at time of operation.…”