Abstract
Diabetes is known to increase blood platelet activity. Activities of pyruvate dehydrogenase
(PDH), adenosine triphosphate (ATP)-citrate lyase (ATPCL), acetyl-coenzyme A (acetyl-CoA)
content, malonyl dialdehyde (MDA), synthesis, and platelet aggregation in resting
conditions and after activation with thrombin were measured in diabetic subjects and
in age- and sex-matched healthy subjects. Activities of ATPCL and PDH, acetyl-CoA
content, and thrombin-evoked MDA synthesis as well as platelet aggregation in diabetes
were 31%, 51%, 62%, 35%, and 21%, respectively, higher than in healthy subjects. In
addition, activation of diabetic platelets caused 2 times greater release of acetyl-CoA
from their mitochondria than in controls. Both 1.0 mmol/L (−)hydroxycitrate and 0.1
mmol/L SB-204490 decreased acetyl-CoA content in platelet cytoplasm along with suppression
of MDA synthesis and platelet aggregation. These inhibitory effects were about 2 times
greater in diabetic than in control platelets. The data presented indicate that the
ATPCL pathway is operative in human platelets and may be responsible for provision
of about 50% of acetyl units from their mitochondrial to cytoplasmic compartment.
Increased acetyl-CoA synthesis in diabetic platelets may be the cause of their excessive
activity in the course of the disease. ATPCL may be a target for its specific inhibitors
as factors decreasing platelet activity.
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Article info
Publication history
Accepted:
July 2,
2003
Received:
March 24,
2003
Footnotes
☆Supported by the Committee for Scientific Research Projects No. 4P05A 086 15, 3P05B 082 23, and W-78 from the Medical University of Gdańsk.
Identification
Copyright
© 2004 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
