Monoglyceride Lipase Deficiency Is Associated with Altered Thrombogenesis in Mice.

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 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.

SUBMITTER: Goeritzer M 

PROVIDER: S-EPMC9958834 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature