Summary
Deep vein thrombosis (DVT) can give rise to chronic debilitating complications, which
are expensive to treat. Anticoagulation, the standard therapy for DVT, prevents propagation,
but does not remove the existing thrombus, which undergoes slow natural resolution.
Alternative forms of treatment that accelerate resolution may arise from a better
understanding of the cellular and molecular pathways that regulate the natural resolution
of thrombi. This review will outline our current understanding of the mechanisms of
thrombus resolution and the role of neovascularisation in this process. Novel experimental
treatments that may one day find clinical use are also discussed. The process of thrombus
resolution resembles wound healing. The mainly monocytic inflammatory infiltrate,
which develops, is associated with the appearance of vascular channels. These cells
may drive resolution by encouraging angiogenesis, which contributes to restoration
of the vein lumen. Significant numbers of bone marrow-derived progenitor cells have
also been found in naturally resolving thrombi, but their precise phenotype and their
role in thrombus recanalisation is unclear. Enhanced thrombus neovascularisation and
rapid vein recanalisation have been achieved in experimental models with proangiogenic
agents. Recent reports of the role of bone marrow-derived progenitor cells in the
revascularisation of ischaemic tissues suggest that it may be possible to obtain the
same effect by delivering pluripotent or lineage specific stem cells into thrombus.
These cells could contribute to thrombus recanalisation by expressing a variety of
proangiogenic cytokines or by lining the new vessels that appear within the thrombus.
Keywords
Deep vein thrombosis - angiogenesis - gene therapy