Lipid peroxidation by activated platelets: A possible link between thrombosis and atherogenesis

• Published in: Atherosclerosis Vol. 115; no. 1; pp. 121 - 128
• Main Authors: Gorog, Peter, Kovacs, Iren B
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.05.1995; Elsevier
• Subjects: Arteriosclerosis - blood; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood Platelets - drug effects; Blood Platelets - physiology; Cardiology. Vascular system; Humans; In Vitro Techniques; Lipid Peroxidation; Lipoproteins, LDL - blood; Luminescent Measurements; Medical sciences; Platelet Activation; Platelets; Reactive Oxygen Species; Stress, Mechanical; Thrombin - pharmacology; Thrombosis - blood; Lipid peroxidation; Platelets; Atherosclerosis; Vascular disease; Human; Platelet; Fluorescence; Cardiovascular disease; Exploration; Lipids; Activation; Chemiluminescence; Densitometry; Peroxidation
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/0021-9150(94)05506-E

Generation of reactive oxygen species (ROS) by platelets was detected by a cyano-tetrazolium dye (CTC) which forms fluorescent formazan on the cell surface upon reduction. Fluorescence was quantitated by a densitometric device. Resting platelets in plasma produced significant fluorescence ( P < 0.0001), and addition of thrombin enhanced the fluorescence of the coagulated platelet mass even further (by 2 h, a 6- and 8-fold increase over fluorescence of platelet-free plasma was measured, respectively). Blood containing CTC was perfused through a glass capillary tubing and the action of shear forces resulted in the formation of an occlusive platelet thrombus. Such thrombi (formed either from whole blood or platelet-rich plasma) were intensely fluorescent, indicating formation of ROS in the platelet mass (a 10- and 8-fold increase in fluorescence over coagulated plasma, respectively). Lipid peroxide content of resting platelets in platelet-rich plasma was doubled over 24 h storage, while addition of thrombin caused a 7.4-fold increase ( P < 0.0001) of lipid peroxides in the retracted platelet-rich plasma-clot. Transition metal chelator and antioxidant prevented lipid peroxidation by platelets in response to thrombin. Thrombin activation of (washed) platelets in plasma-free medium caused only 1.4-fold increase in oxidation of added low density lipoprotein (LDL). In contrast, thrombin activation of platelets suspended in de-lipidated autologous plasma resulted in a 5.25-fold increase ( P < 0.0001) in LDL oxidation. Generation of ROS and lipid peroxides by platelets can be an important mechanism through which thrombotic events contribute to atherogenesis.