Monoglyceride Lipase Deficiency Is Associated with Altered Thrombogenesis in Mice
(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.
(Less)
- author
- publishing date
- 2023-02-04
- 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}}, }