Enhanced platelet adherence and aggregation in Chagas' disease: a potential pathogenic mechanism for cardiomyopathy.
Spasm and thrombosis of the coronary microcirculation has been implicated in the pathogenesis of the cardiomyopathy of Chagas' disease. We demonstrate that increases in platelet adherence and aggregation accompany Trypanosoma cruzi infection and may contribute to the observed microvascular pathology. Scanning electron microscopy and radiolabeled platelets studies revealed that platelet adherence to T. cruzi-infected human endothelial cells was significantly increased when compared to controls (P = 0.024). In in vitro experiments, we determined the influence of infection on prostacyclin production, a marker of endothelial cell perturbation. The basal levels of 6-keto-prostaglandin F1 alpha was significantly greater in the supernatant of infected endothelial cells than in those of uninfected endothelial cells (P less than 0.05). The influence of infection was assessed on platelet aggregation at days 5 and 12 post-infection in A/J mice. Platelets from T. cruzi-infected mice were 2-6-fold more sensitive to aggregation induced by adenosine diphosphate and sodium arachidonate than controls. Thromboxane B2 levels in the plasma of infected mice were greater than controls. These data support the hypothesis that heightened platelet reactivity and endothelial cell dysfunction are associated with acute Chagas' disease and may cause coronary microvascular spasm and/or occlusion.
Tanowitz
H B
HB
Albert Einstein College of Medicine, Bronx, New York.
Burns
E R
ER
Sinha
A K
AK
Kahn
N N
NN
Morris
S A
SA
Factor
S M
SM
Hatcher
V B
VB
Bilezikian
J P
JP
Baum
S G
SG
Wittner
M
M
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000648:ultrastructure; D002478:Cells, Cultured; D002598:Chagas Cardiomyopathy / Q000209:etiology*; D014355:Chagas Disease / Q000097:blood*; D003331:Coronary Vessels / Q000469:parasitology; D004730:Endothelium, Vascular / Q000166:cytology; D011464:Epoprostenol / Q000032:analysis; D005260:Female; D006801:Humans; D051379:Mice; D008833:Microcirculation / Q000469:parasitology; D008855:Microscopy, Electron, Scanning; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D013929:Thromboxane B2 / Q000032:analysis
D013929:Thromboxane B2; D011464:Epoprostenol