Screening a collection of fungal extracts for new medicinal compounds in the treatment of vascular disease

Abstract

Vascular disease due to atherosclerosis is the leading cause of morbidity and mortality in Western societies. The actual cause of death in these situations is myocardial infarction or stroke, and is due to blockage of the coronary or cerebral arteries, respectively, by a platelet clot known as a thrombus. In order for a thrombus to form, the blood vessel wall must be damaged, as in the rupture or erosion of an atherosclerotic plaque, exposing a surface to which platelets adhere, become active, and aggregate. Currently, persons at risk for cardiovascular disease use aspirin to prevent platelet activation and those who have had a heart attack or stroke are placed on clopidogrel (Plavix) to further inhibit platelet activation. Since many patients are becoming resistant to these treatments, the search for new inhibitors of platelet activation is necessary. Conversely, patients may be placed on warfarin (Coumadin) to prevent blood coagulation by inhibiting the actions of thrombin; warfarin therapy requires very close monitoring. Given the drawbacks to medicines currently in use, the search for new drugs is imperative. The search for fungal inhibitors of thrombus formation seems logical, since the use of fungi for medicinal purposes has been well documented, particularly in Asian countries. However, little is known about the actual compounds in fungi exerting a biological effect. In this study, a large collection of fungal extracts was screened to determine activity against both platelet aggregation and blood coagulation.