Thromboxane A2 and prostacyclin generation in the microvasculature of patients with atherosclerosis--effect of low-dose aspirin.
Generation of thromboxane A2 (TxA2) and prostacyclin (PGI2) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the microvasculature made to determine skin bleeding time was investigated in 7 patients with atherosclerosis (angiographically verified obstructions of the femoral arteries) and in 7 normal control subjects apparently free of atherosclerotic lesions. Similar amounts of TxA2 (measured as thromboxane B2, TxB2) were generated at the site of plug formation in the patients with peripheral vascular disease (PVD) and in the control subjects. Significantly lower levels of PGI2 (measured as 6-keto-prostaglandin F1 alpha, 6-keto-PGF1 alpha) were found in blood from an injury of the microvasculature in the patients compared with the controls. These data do not suggest a major role of the platelet prostaglandin metabolism in the development of atherosclerosis. However, decreased synthesis of PGI2 by endothelial cells might contribute to the development and/or progression of atherosclerotic lesions. In the patients with PVD, low-dose aspirin (50 mg/day for 7 days) resulted in a greater than 90% inhibition of the TxB2 production at the site of plug formation. Following low-dose aspirin 6-keto-PGF1 alpha levels were below 20 pg/ml (limit of sensitivity of our radioimmunoassay procedure) in the majority of the samples. We therefore conclude that in patients with PVD a decreased synthesis of PGI2 by endothelial cells might contribute to the progression of atherosclerosis. Furthermore, low-dose aspirin treatment results in a similar inhibition of the platelet prostaglandin generation as recently observed in healthy subjects.
Kyrle
P A
PA
Department of Internal Medicine I, University of Vienna, Austria.
Minar
E
E
Brenner
B
B
Eichler
H G
HG
Heistinger
M
M
Marosi
L
L
Lechner
K
K
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000368:Aged; D001161:Arteriosclerosis / Q000097:blood*; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000378:metabolism; D008875:Middle Aged; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000097:blood
D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D001241:Aspirin