The increase of adenylate kinase activity in the blood can control aggregation of platelets in coronary or peripheral arterial ischemia

Activation and aggregation of blood platelets is crucial for hemostasis and thrombosis. In the vascular system adenine nucleotides are important signaling molecules playing a key role in hemostasis. ADP was the first low molecular weight agent recognized to cause blood platelets activation and aggregation. NTPDases and adenylate kinase (AK) are the main enzymes involved in metabolism of extracellular adenine nucleotides. The majority of studies concentrated on the role of NTPDase1 (apyrase) in the inhibition of platelets aggregation. Up to now, there are still insufficient data concerning the role of AK in this process. We found that adenylate kinase activity in the serum of patients with myocardial infarction is significantly increased when compared to the healthy volunteers. The elevated activity of AK is connected to appearance of another isoform of that enzyme, expressed in patients with myocardial infarction. The influence of AK on the pig blood platelets aggregation induced by 20 μM ADP or 7.5 μg/ml rat collagen was examined. 1U of adenylate kinase added to platelet-rich plasma (PRP) before ADP or collagen, inhibited the platelets aggregation. One minute after induction of platelets activation by ADP as much as 5U of adenylate kinase was necessary to stop the platelet aggregation. In the case of collagen activated aggregation, only 2U of AK added 1 or 5 minutes after initiation of the aggregation process were sufficient for disaggregation of platelets. The increase of ATP: ADP ratio is probably responsible for the initiation of disaggregation process. We conclude that adenylate kinase is involved in regulation of plate-lets aggregation. Anticoagulative role of AK indicates the possibility of using this enzyme in the treatment of cardiovascular diseases.