Adipose Triglyceride Lipase Deficiency Attenuates In Vitro Thrombus Formation without Affecting Platelet Activation and Bleeding In Vivo.

Autor: Goeritzer M; Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria., Schlager S; Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria.; AOP Orphan Pharmaceuticals GmbH, 1190 Vienna, Austria., Kuentzel KB; Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria., Vujić N; Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria., Korbelius M; Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria., Rainer S; Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria., Kolb D; Core Facility Ultrastructural Analysis, Medical University of Graz, 8010 Graz, Austria.; BioTechMed-Graz, 8010 Graz, Austria., Mussbacher M; Department of Pharmacology and Toxicology, University of Graz, 8010 Graz, Austria., Salzmann M; Department of Internal Medicine II/Cardiology, Medical University of Vienna, 1190 Vienna, Austria., Schrottmaier WC; Institute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1190 Vienna, Austria., Assinger A; Institute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1190 Vienna, Austria., Schlagenhauf A; Department of General Pediatrics and Adolescent Medicine, Medical University of Graz, 8010 Graz, Austria., Madreiter-Sokolowski CT; Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria., Blass S; Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria., Eichmann TO; BioTechMed-Graz, 8010 Graz, Austria.; Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.; Core Facility Mass Spectrometry, Medical University of Graz, 8010 Graz, Austria., Graier WF; Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria.; BioTechMed-Graz, 8010 Graz, Austria., Kratky D; Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria.; BioTechMed-Graz, 8010 Graz, Austria.
Jazyk: angličtina
Zdroj: Cells [Cells] 2022 Mar 01; Vol. 11 (5). Date of Electronic Publication: 2022 Mar 01.
DOI: 10.3390/cells11050850
Abstrakt: According to genome-wide RNA sequencing data from human and mouse platelets, adipose triglyceride lipase (ATGL), the main lipase catalyzing triglyceride (TG) hydrolysis in cytosolic lipid droplets (LD) at neutral pH, is expressed in platelets. Currently, it is elusive to whether common lipolytic enzymes are involved in the degradation of TG in platelets. Since the consequences of ATGL deficiency in platelets are unknown, we used whole-body and platelet-specific (plat)Atgl-deficient (-/-) mice to investigate the loss of ATGL on platelet function. Our results showed that platelets accumulate only a few LD due to lack of ATGL. Stimulation with platelet-activating agonists resulted in comparable platelet activation in Atgl-/-, platAtgl-/-, and wild-type mice. Measurement of mitochondrial respiration revealed a decreased oxygen consumption rate in platelets from Atgl-/- but not from platAtgl-/- mice. Of note, global loss of ATGL was associated with an anti-thrombogenic phenotype, which was evident by reduced thrombus formation in collagen-coated channels in vitro despite unchanged bleeding and occlusion times in vivo. We conclude that genetic deletion of ATGL affects collagen-induced thrombosis without pathological bleeding and platelet activation.
Databáze: MEDLINE
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