Platelet Integrin αIIbβ3 Inhibitor Rescues Progression of Apoptosis in Human Platelets.
BACKGROUND Apoptosis plays an important role in the physiology of platelet function. We aimed to detect the effect of the platelet integrin αIIbβ3 inhibitor, tirofiban, on apoptotic events, including mitochondrial inner-membrane potential (ΔΨm), phosphatidylserine (PS) exposure on platelet surface, and the generation of reactive oxygen species (ROS), when washed platelets were stimulated with thrombin. MATERIAL AND METHODS The study included washed platelets from healthy humans, divided into 4 groups: vehicle, and tirofiban (0.05 μg/ml, 0.25 μg/ml, and 0.5 μg/ml). Platelets were pretreated with vehicle or tirofiban and incubated at 37°C with agitation for 6 h and 24 h. Before thrombin addition, the vehicle group divided into 2 equal groups. Except one vehicle group, the other 4 groups were all stimulated with thrombin (1 U/ml) for 30 min at 37°C. Using flow cytometry, we studied the DYm and PS exposure on platelet surfaces, and the generation of ROS in platelets. RESULTS We observed that at the time of 6 h and 24 h, thrombin-stimulated vehicle platelets induced significant depo-larization of ΔΨm, higher PS exposure, and increased ROS production compared with the vehicle group (P<0.01). However, the tirofiban group had significantly more recovery of DYm, PS exposure, and ROS production compared with the thrombin group (P<0.01). CONCLUSIONS The platelet integrin αIIbβ3 inhibitor, tirofiban, inhibits the depolarization of DYm, PS exposure on platelet surface, and ROS production when stimulated with thrombin. These results suggest that αIIbβ3 inhibitor inhibits the initiation of apoptosis in platelets, showing a potential clinical application of tirofiban as an apoptosis inhibitor.
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland).
Jie
J
Zhu
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland).
Qinghang
Q
Wang
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland).
Yumei
Y
Nie
Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, Jiangsu, China (mainland).
Rong
R
Yan
Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Healt, Suzhou, Jiangsu, China (mainland).
Kesheng
K
Dai
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland).
Birong
B
Zhou
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017382:Reactive Oxygen Species; D014443:Tyrosine; D013917:Thrombin; D000077466:Tirofiban