Abstract
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.
Highlights
Platelets are small anucleated blood cells, which are derived from megakaryocytes in the bone marrow
All agonists tested (ADP, protease-activated receptor 4 agonist peptide AYPGKF-NH2 (PAR4-AP), collagenrelated peptide-XL (CRP), and CVX) showed comparable results between the genotypes (Figure 3C–F), suggesting that platelet activation can be maintained in the absence of adipose triglyceride lipase (ATGL)
Express only ATGL and monoglyceride lipase (MGL) but not Hormone-sensitive lipase (HSL) protein. Consistent with these data, genome-wide RNA sequencing showed that Mgl and Atgl are highly expressed in human platelets, whereas Hsl is expressed only at low levels [26]
Summary
Platelets are small anucleated blood cells, which are derived from megakaryocytes in the bone marrow. Platelets release numerous mediators that lead to the recruitment of leukocytes and progenitor cells to sites of vascular injury and inflammation. In this way, platelets are involved in the etiology of various diseases, such as diabetes, atherothrombosis, cardiovascular and autoimmune diseases [1–4]. Platelet activation is amplified by soluble agonists such as adenosine diphosphate (ADP), thromboxane A2 (TXA2), or thrombin, which mediate their action via G-protein-coupled receptors [6]. These events provide a stimulus for the conformational change of platelet αIIbβ integrin (GPIIb/IIIa receptor), which (in its activated form) can bind fibrinogen and vWF, thereby triggering platelet aggregation and stable thrombus formation [6,7]. We hypothesized that ATGL deficiency may affect platelet function
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