Abstract 226: Platelet Mitochondria Regulate Thrombotic and Inflammatory Function
Introduction: Cells require energy provided by glycolytic and mitochondrial sources. Obesity, a health issue worldwide, affects mitochondrial function. Platelets possess mitochondria although their role in platelet function is unclear. We assessed the hypothesis that platelet mitochondria contribute to cellular processes and the mitochondrial disorder in obesity may also affect platelet functions.
Methods: Platelet aggregation and adhesion were assessed to estimate the effects of selective metabolic inhibitors on platelet functions. Mitochondrial ultrastructure was analyzed by transmission electron microscopy in the presence of these inhibitors. C57BL/6J mice were used to investigate the mitochondrial contribution to the effects of high fat diet (HFD) on platelet adhesion. mRNA expression in mouse platelets was measured by RT-PCR.
Results: The disruption of the mitochondrial function by complementary inhibitors resulted in a reduction of platelet aggregation to 80.9 ± 7.7% (antimycin A), 77.5 ± 9.5% (oligomycin), 59.1 ± 3.2% (carbonyl cyanide 3-chlorophenylhydrazone, CCCP), and 37.2 ± 4.3% (potassium cyanide); n=3, p<0.0001. Significant morphological changes in platelet mitochondria, including mitochondrial cristae swelling and accumulation of dense masses in the presence of metabolic inhibitors oligomycin and CCCP were observed. A HFD enhanced thrombin-induced platelet adhesion (44.2 ± 8.7% vs normal chow 30.6 ± 1.3%), which was abrogated in the presence of metabolic inhibitors (19.4 ± 7.1% vs normal chow 14.6 ± 5.4% in the presence of oligomycin; 4.5 ± 2.1% vs normal chow 6.6 ± 2.0% in the presence of CCCP; n=7, p<0.001). Mitochondrial, inflammatory, and thrombotic transcripts were all affected in platelets by a HFD. Expression of mitochondrial (mitofusin 2)- and thrombotic (CD41)-related genes were downregulated, while inflammatory-related genes TLR2 and IL1R1 were upregulated in mouse platelets after 3 weeks of a HFD. In conclusion, platelet mitochondria maintain homeostasis and regulate thrombotic and inflammatory function. Mitochondrial dysfunction in obesity affects platelet function, potentially contributing to cardiovascular disease risks associated with the metabolic syndrome.
- © 2012 by American Heart Association, Inc.