Abstract Number: PB1694
Meeting: ISTH 2020 Congress
Background: In platelets, the presence of cytosolic lipid droplets and the role of their lipolytic machinery to degrade triglycerides are still elusive. According to genome-wide RNA-sequencing data from human platelets, adipose triglyceride lipase (ATGL) and monoglyceride lipase (MGL) are expressed in platelets, but their role in platelet function is unknown.
Aims: Our aim is to examine the potential role of ATGL and MGL in platelet physiology.
Methods: We used whole-body and platelet-specific Atgl- and Mgl-knock-out (-/-) mice to study the role of ATGL and MGL in platelets. We visualized platelet spreading and morphology by electron microscopy. We determined platelet activation by measuring the expression of P-selectin and activated glycoprotein IIb/IIIa by flow cytometry and investigated mitochondrial respiration using a Seahorse XF analyzer. We performed bleeding assays to study hemostatic function and determined platelet aggregation using a Multiplate analyzer.
Results: Atgl-/- platelets do not accumulate lipid droplets as observed in other cells and tissues and have unchanged platelet activation. We found reduced mitochondrial respiration in platelets of whole-body Atgl-/- mice, however, oxygen consumption rate of platelets isolated from platelet-specific Atgl-/- mice was unchanged. Of note, the global loss of MGL in mice was associated with a decreased hemostatic function, as evident by an increased bleeding time. Moreover, platelet activation in Mgl-/- blood was significantly decreased in response to collagen-related peptide and convulxin, which was unaltered in platelet-specific Mgl-/- mice. Platelet aggregation in response to collagen was unchanged in all genotypes.
Conclusions: We conclude that the global, but not the platelet-specific loss of either ATGL or MGL affects platelet function in mice, which might be attributable to factors in the circulation.
To cite this abstract in AMA style:Goeritzer M, Schlager S, Vujic N, Rainer S, Kolb D, Mussbacher M, Schlagenhauf A, Haidl H, Madreiter-Sokolowski CT, Graier WF, Kratky D. Novel Role for Intracellular Lipases in Platelets [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/novel-role-for-intracellular-lipases-in-platelets/. Accessed December 5, 2021.
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