Adipose Triglyceride Lipase Deficiency Attenuates In Vitro Thrombus Formation without Affecting Platelet Activation and Bleeding In Vivo.
adipose triglyceride lipase
intravital microscopy
mitochondrial respiration
platelets
thrombosis
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
01 03 2022
01 03 2022
Historique:
received:
02
02
2022
revised:
24
02
2022
accepted:
25
02
2022
entrez:
10
3
2022
pubmed:
11
3
2022
medline:
12
4
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35269472
pii: cells11050850
doi: 10.3390/cells11050850
pmc: PMC8908992
pii:
doi:
Substances chimiques
Triglycerides
0
Acyltransferases
EC 2.3.-
Lipase
EC 3.1.1.3
PNPLA2 protein, mouse
EC 3.1.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Austrian Science Fund FWF
ID : P 30882
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : W 1226
Pays : Austria
Références
J Biol Chem. 2011 Mar 4;286(9):7418-28
pubmed: 21196579
Eur J Clin Invest. 1994 Feb;24 Suppl 1:30-3
pubmed: 8013529
Prog Cardiovasc Dis. 1987 Jul-Aug;30(1):61-72
pubmed: 3299492
J Biol Chem. 2020 Apr 17;295(16):5307-5320
pubmed: 32161117
J Biol Chem. 2004 Aug 6;279(32):34032-7
pubmed: 15163665
Nat Med. 2011 Aug 21;17(9):1076-85
pubmed: 21857651
J Leukoc Biol. 2015 Nov;98(5):837-50
pubmed: 26109679
Blood. 2016 Apr 21;127(16):1949-53
pubmed: 26929273
Cardiovasc Diabetol. 2018 Aug 31;17(1):121
pubmed: 30170601
Pathophysiol Haemost Thromb. 2006;35(3-4):346-54
pubmed: 16877882
Cardiovasc Res. 1999 Feb;41(2):450-7
pubmed: 10341844
Circ Res. 2014 Mar 28;114(7):1185-203
pubmed: 24677238
Blood. 2004 Dec 1;104(12):3611-7
pubmed: 15308568
J Thromb Haemost. 2011 Sep;9(9):1862-3
pubmed: 21884567
Circ Res. 2006 Dec 8;99(12):1293-304
pubmed: 17158345
Hematology Am Soc Hematol Educ Program. 2011;2011:51-61
pubmed: 22160012
Cardiovasc Diagn Ther. 2017 Dec;7(Suppl 3):S207-S218
pubmed: 29399524
J Biol Chem. 2010 Jun 25;285(26):20192-201
pubmed: 20424161
J Lipid Res. 2008 May;49(5):1137-46
pubmed: 18281723
Cell Death Dis. 2012 Mar 15;3:e280
pubmed: 22419109
J Clin Invest. 1969 Nov;48(11):2114-23
pubmed: 4309956
J Thromb Haemost. 2011 Apr;9(4):779-89
pubmed: 21261806
Nat Commun. 2016 Nov 15;7:13464
pubmed: 27845343
World J Exp Med. 2012 Apr 20;2(2):30-6
pubmed: 24520531
Platelets. 1999;10(6):357-67
pubmed: 16801115
J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Mar 1;951-952:119-28
pubmed: 24548922
Biochem Soc Trans. 2017 Dec 15;45(6):1213-1223
pubmed: 29054925
Cell Mol Life Sci. 2011 Dec;68(23):3933-47
pubmed: 21533980
Cell Rep. 2019 Jul 23;28(4):896-908.e5
pubmed: 31340152
Am J Cardiovasc Drugs. 2005;5(6):399-408
pubmed: 16259528
J Biol Chem. 1982 Oct 10;257(19):11278-83
pubmed: 7118885
J Thromb Haemost. 2009 Nov;7(11):1759-66
pubmed: 19691483
J Cell Biol. 2013 Jun 10;201(6):785-96
pubmed: 23751492
Blood Rev. 2015 May;29(3):153-62
pubmed: 25468720
Front Cardiovasc Med. 2019 Oct 29;6:153
pubmed: 31737646
Science. 2006 May 5;312(5774):734-7
pubmed: 16675698
J Biol Chem. 2016 Jan 8;291(2):913-23
pubmed: 26565024
Platelets. 2018 Jun;29(4):357-364
pubmed: 29461915
Nat Genet. 2007 Jan;39(1):28-30
pubmed: 17187067
J Clin Invest. 1975 Mar;55(3):636-43
pubmed: 1117069
Arterioscler Thromb Vasc Biol. 1995 Jun;15(6):759-64
pubmed: 7773730
Nat Rev Mol Cell Biol. 2017 Nov;18(11):671-684
pubmed: 28852221
Transfusion. 2010 Aug;50(8):1665-76
pubmed: 20158687
Biochim Biophys Acta. 1984 May 11;793(3):416-22
pubmed: 6712978
Blood. 2003 Jul 15;102(2):449-61
pubmed: 12649139
Blood. 2011 Oct 6;118(14):e101-11
pubmed: 21596849
J Biol Chem. 2004 Nov 19;279(47):48968-75
pubmed: 15364929
J Clin Invest. 1969 Jan;48(1):156-64
pubmed: 5765018
J Thromb Haemost. 2018 Nov;16(11):2300-2314
pubmed: 30151891
Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):67-73
pubmed: 21030715
Cold Spring Harb Perspect Biol. 2012 Feb 01;4(2):
pubmed: 21937733
Anal Chem. 2015 Jan 6;87(1):413-21
pubmed: 25439269
Transfus Med Rev. 2020 Apr;34(2):108-116
pubmed: 31987597
Blood. 2014 Apr 17;123(16):e37-45
pubmed: 24523238