Prevention and treatment of thrombosis: novel strategies arising from our understanding the healthy endothelium.
The strategies used to prevent and treat thrombosis are based on our understanding of how to ameliorate the pathophysiological responses to injury, such as using inhibitors of platelet activation and inhibitors of coagulation. Both platelets and the coagulation pathway are activated in response to injury. An alternative strategy which has not been investigated to the same extent, is to use substances which contribute to the biocompatibility of blood and vessel wall which predominate under normal conditions. This latter strategy exploits the concept of restoring blood/vessel wall compatibility without risk of bleeding such as can occur when platelets as rendered haemostatically defective (antiplatelet therapies) or maintaining the patient hypocoagulated (anticoagulant therapies). Recent studies suggest that by better understanding the biocompatibility of the healthy endothelium with blood, we may be able to identify those substances which contribute to blood/vessel wall biocompatibility in the healthy environment, and subsequently which may achieve effective antithrombotic therapy with minimal risk of bleeding side-effects. In this review, we identify three such substances all of which are produced by the blood vessel wall. These agents are 13-hydroxyoctadecadienoic acid (13-HODE), a lipoxygenase metabolite of linoleic acid, and two glycosaminoglycans, heparan sulfate and dermatan sulfate.
Buchanan
M R
MR
McMaster University, Department of Pathology, Hamilton, Ontario, Canada.
Brister
S J
SJ
Ofosu
F
F
D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D003871:Dermatan Sulfate / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D011464:Epoprostenol / Q000502:physiology; D006487:Hemostasis / Q000502:physiology*; D006497:Heparan Sulfate / Q000502:physiology; D006801:Humans; D008041:Linoleic Acids / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology; D013927:Thrombosis / Q000503:physiopathology / Q000517:prevention & control*
D000991:Antithrombins; D003871:Dermatan Sulfate; D011464:Epoprostenol; D006497:Heparan Sulfate; D008041:Linoleic Acids; D009569:Nitric Oxide; C024348:13-hydroxy-9,11-octadecadienoic acid