Recombinant Apyrase (AZD3366) Against Myocardial Reperfusion Injury.
Adenosine
Animal model
Apyrase
Infarct size
Myocardial infarction
Necroptosis
Necrosis
Pyroptosis
Journal
Cardiovascular drugs and therapy
ISSN: 1573-7241
Titre abrégé: Cardiovasc Drugs Ther
Pays: United States
ID NLM: 8712220
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
accepted:
17
02
2022
medline:
3
8
2023
pubmed:
23
2
2022
entrez:
22
2
2022
Statut:
ppublish
Résumé
Recombinant apyrase (AZD3366) increases adenosine production and ticagrelor inhibits adenosine reuptake. We investigated whether intravenous AZD3366 before reperfusion reduces myocardial infarct size (IS) and whether AZD3366 and ticagrelor have additive effects. Sprague-Dawley rats underwent 30 min ischemia. At 25 min of ischemia, animals received intravenous AZD3366 or vehicle. Additional animals received intravenous CGS15943 (an adenosine receptor blocker) or intraperitoneal ticagrelor. At 24 h reperfusion, IS was assessed by triphenyltetrazolium chloride. Other rats were subjected to 30 min ischemia followed by 1 h or 24 h reperfusion. Myocardial samples were assessed for adenosine levels, RT-PCR, and immunoblotting. AZD3366 and ticagrelor reduced IS. The protective effect was blocked by CGS15943. The effect of AZD3366 + ticagrelor was significantly greater than AZD3366. One hour after infarction, myocardial adenosine levels significantly increased with AZD3366, but not with ticagrelor. In contrast, 24 h after infarction, adenosine levels were equally increased by AZD3366 and ticagrelor, and levels were higher in the AZD3366 + ticagrelor group. One hour after reperfusion, AZD3366 and ticagrelor equally attenuated the increase in interleukin-15 (an early inflammatory marker after ischemic cell death) levels, and their combined effects were additive. AZD3366, but not ticagrelor, significantly attenuated the increase in RIP1, RIP3, and P-MLKL (markers of necroptosis) 1 h after reperfusion. AZD3366, but not ticagrelor, significantly attenuated the increase in IL-6 and GSDMD-N (markers of pyroptosis) 1 h after reperfusion. At 24 h of reperfusion, both agents equally attenuated the increase in these markers, and their effects were additive. AZD3366 attenuated inflammation, necrosis, necroptosis, and pyroptosis and limited IS. The effects of AZD3366 and ticagrelor were additive.
Identifiants
pubmed: 35192075
doi: 10.1007/s10557-022-07329-9
pii: 10.1007/s10557-022-07329-9
doi:
Substances chimiques
Apyrase
EC 3.6.1.5
Ticagrelor
GLH0314RVC
Adenosine
K72T3FS567
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
625-646Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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