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Monoglyceride Lipase Deficiency Is Associated with Altered Thrombogenesis in Mice

Goeritzer, Madeleine ; Kuentzel, Katharina B LU orcid ; Beck, Sarah ; Korbelius, Melanie ; Rainer, Silvia ; Bradić, Ivan ; Kolb, Dagmar ; Mussbacher, Marion ; Schrottmaier, Waltraud C and Assinger, Alice , et al. (2023) In International Journal of Molecular Sciences 24(4).
Abstract

Monoglyceride lipase (MGL) hydrolyzes monoacylglycerols (MG) to glycerol and one fatty acid. Among the various MG species, MGL also degrades 2-arachidonoylglycerol, the most abundant endocannabinoid and potent activator of the cannabinoid receptors 1 and 2. We investigated the consequences of MGL deficiency on platelet function using systemic (Mgl-/-) and platelet-specific Mgl-deficient (platMgl-/-) mice. Despite comparable platelet morphology, loss of MGL was associated with decreased platelet aggregation and reduced response to collagen activation. This was reflected by reduced thrombus formation in vitro, accompanied by a longer bleeding time and a higher blood volume loss. Occlusion time after FeCl3-induced injury was markedly... (More)

Monoglyceride lipase (MGL) hydrolyzes monoacylglycerols (MG) to glycerol and one fatty acid. Among the various MG species, MGL also degrades 2-arachidonoylglycerol, the most abundant endocannabinoid and potent activator of the cannabinoid receptors 1 and 2. We investigated the consequences of MGL deficiency on platelet function using systemic (Mgl-/-) and platelet-specific Mgl-deficient (platMgl-/-) mice. Despite comparable platelet morphology, loss of MGL was associated with decreased platelet aggregation and reduced response to collagen activation. This was reflected by reduced thrombus formation in vitro, accompanied by a longer bleeding time and a higher blood volume loss. Occlusion time after FeCl3-induced injury was markedly reduced in Mgl-/- mice, which is consistent with contraction of large aggregates and fewer small aggregates in vitro. The absence of any functional changes in platelets from platMgl-/- mice is in accordance with lipid degradation products or other molecules in the circulation, rather than platelet-specific effects, being responsible for the observed alterations in Mgl-/- mice. We conclude that genetic deletion of MGL is associated with altered thrombogenesis.

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publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Mice, Endocannabinoids/metabolism, Lipolysis, Mice, Inbred C57BL, Mice, Knockout, Monoacylglycerol Lipases/genetics, Monoglycerides
in
International Journal of Molecular Sciences
volume
24
issue
4
article number
3116
publisher
MDPI AG
external identifiers
  • scopus:85148997691
  • pmid:36834530
ISSN
1422-0067
DOI
10.3390/ijms24043116
language
English
LU publication?
no
id
8e28f844-9b2f-4a2c-8b56-312f0e2f1278
date added to LUP
2023-03-03 11:21:10
date last changed
2024-04-19 20:20:45
@article{8e28f844-9b2f-4a2c-8b56-312f0e2f1278,
  abstract     = {{<p>Monoglyceride lipase (MGL) hydrolyzes monoacylglycerols (MG) to glycerol and one fatty acid. Among the various MG species, MGL also degrades 2-arachidonoylglycerol, the most abundant endocannabinoid and potent activator of the cannabinoid receptors 1 and 2. We investigated the consequences of MGL deficiency on platelet function using systemic (Mgl-/-) and platelet-specific Mgl-deficient (platMgl-/-) mice. Despite comparable platelet morphology, loss of MGL was associated with decreased platelet aggregation and reduced response to collagen activation. This was reflected by reduced thrombus formation in vitro, accompanied by a longer bleeding time and a higher blood volume loss. Occlusion time after FeCl3-induced injury was markedly reduced in Mgl-/- mice, which is consistent with contraction of large aggregates and fewer small aggregates in vitro. The absence of any functional changes in platelets from platMgl-/- mice is in accordance with lipid degradation products or other molecules in the circulation, rather than platelet-specific effects, being responsible for the observed alterations in Mgl-/- mice. We conclude that genetic deletion of MGL is associated with altered thrombogenesis.</p>}},
  author       = {{Goeritzer, Madeleine and Kuentzel, Katharina B and Beck, Sarah and Korbelius, Melanie and Rainer, Silvia and Bradić, Ivan and Kolb, Dagmar and Mussbacher, Marion and Schrottmaier, Waltraud C and Assinger, Alice and Schlagenhauf, Axel and Rost, René and Gottschalk, Benjamin and Eichmann, Thomas O and Graier, Wolfgang F and Vujić, Nemanja and Kratky, Dagmar}},
  issn         = {{1422-0067}},
  keywords     = {{Animals; Mice; Endocannabinoids/metabolism; Lipolysis; Mice, Inbred C57BL; Mice, Knockout; Monoacylglycerol Lipases/genetics; Monoglycerides}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{4}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Monoglyceride Lipase Deficiency Is Associated with Altered Thrombogenesis in Mice}},
  url          = {{http://dx.doi.org/10.3390/ijms24043116}},
  doi          = {{10.3390/ijms24043116}},
  volume       = {{24}},
  year         = {{2023}},
}