Abstract:
:Inhibition of either P2Y12 receptor or the nucleotide-binding oligomerization domain- (NOD-) like receptor pyrin domain containing 3 (NLRP3) inflammasome provides cardioprotective effects. Here, we investigate whether direct NLRP3 inflammasome inhibition exerts additive effects on myocardial protection induced by the P2Y12 receptor antagonist Ticagrelor. Ticagrelor (150 mg/kg) was orally administered to rats for three consecutive days. Then, isolated hearts underwent an ischemia/reperfusion (30 min ischemia/60 min reperfusion; IR) protocol. The selective NLRP3 inflammasome inhibitor INF (50 μM) was infused before the IR protocol to the hearts from untreated animals or pretreated with Ticagrelor. In parallel experiments, the hearts isolated from untreated animals were perfused with Ticagrelor (3.70 μM) before ischemia and subjected to IR. The hearts of animals pretreated with Ticagrelor showed a significantly reduced infarct size (IS, 49 ± 3% of area at risk, AAR) when compared to control IR group (69 ± 2% of AAR). Similarly, ex vivo administration of INF before the IR injury resulted in significant IS reduction (38 ± 3% of AAR). Myocardial IR induced the NLRP3 inflammasome complex formation, which was attenuated by either INF pretreatment ex vivo, or by repeated oral treatment with Ticagrelor. The beneficial effects induced by either treatment were associated with the protective Reperfusion Injury Salvage Kinase (RISK) pathway activation and redox defence upregulation. In contrast, no protective effects nor NLRP3/RISK modulation were recorded when Ticagrelor was administered before ischemia in isolated heart, indicating that Ticagrelor direct target is not in the myocardium. Our results confirm that Ticagrelor conditioning effects are likely mediated through platelets, but are not additives to the ones achieved by directly inhibiting NLRP3.
journal_name
Oxid Med Cell Longevjournal_title
Oxidative medicine and cellular longevityauthors
Penna C,Aragno M,Cento AS,Femminò S,Russo I,Bello FD,Chiazza F,Collotta D,Alves GF,Bertinaria M,Zicola E,Mercurio V,Medana C,Collino M,Pagliaro Pdoi
10.1155/2020/9219825subject
Has Abstractpub_date
2020-08-03 00:00:00pages
9219825eissn
1942-0900issn
1942-0994journal_volume
2020pub_type
杂志文章abstract::Almost all human diseases are strongly associated with inflammation, and a deep understanding of the exact mechanism is helpful for treatment. The NLRP3 inflammasome composed of the NLRP3 protein, procaspase-1, and ASC plays a vital role in regulating inflammation. In this review, NLRP3 regulation and activation, its ...
journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章,评审
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章,评审
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章,评审
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章,评审
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更新日期:2019-05-12 00:00:00
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章
doi:10.1155/2018/9658230
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章
doi:10.1155/2017/6487825
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journal_title:Oxidative medicine and cellular longevity
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doi:10.1155/2019/6309465
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章,评审
doi:10.1155/2015/181260
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章
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journal_title:Oxidative medicine and cellular longevity
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abstract::[This corrects the article DOI: 10.1155/2017/6838921.]. ...
journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章,已发布勘误
doi:10.1155/2017/3575348
更新日期:2017-01-01 00:00:00
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章
doi:10.1155/2017/4721352
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章
doi:10.1155/2019/8218650
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章,评审
doi:10.1155/2014/780179
更新日期:2014-01-01 00:00:00
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journal_title:Oxidative medicine and cellular longevity
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journal_title:Oxidative medicine and cellular longevity
pub_type: 杂志文章,评审
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