Integrin-Linked Kinase Activation Prevents Ventricular Arrhythmias Induced by Ischemia/Reperfusion Via Inhibition of Connexin 43 Remodeling.
J Cardiovasc Transl Res
; 14(4): 610-618, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-32144627
ABSTRACT
Ischemia reperfusion (I/R)-induced arrhythmia is a serious complication in patients with cardiac infarction. Remodeling of connexin (Cx) 43, manifested as phosphorylation, contributes significantly to arrhythmogenesis. Integrin-linked kinase (ILK) attenuated ventricular remodeling and improved cardiac function in rats after myocardial infarction. We hypothesized that ILK, through Cx43 phosphorylation, would be protective against I/R-induced ventricular arrhythmias. Our study showed that I/R-induced ventricular arrhythmias were attenuated by an ILK agonist LPTP and worsened by the ILK inhibitor Cpd22. I/R disrupted Cx43 distribution, but it was partially normalized in the presence of LPTP. Compared with I/R, the phosphorylation of Akt was increased significantly after pretreatment with LPTP. The increase in phosphorylated Akt was physiologically significant because, in the presence of the Akt inhibitor MK2206, the protective effects of LPTP were blocked. This indicated that ILK activation prevented I/R-induced-ventricular arrhythmia, an effect potentially related to inhibition of Cx43 remodeling via Akt activation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrilação Ventricular
/
Traumatismo por Reperfusão Miocárdica
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Taquicardia Ventricular
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Proteínas Serina-Treonina Quinases
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Conexina 43
/
Ativadores de Enzimas
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Miócitos Cardíacos
/
Antiarrítmicos
Limite:
Animals
Idioma:
En
Revista:
J Cardiovasc Transl Res
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China