P2Y12 inhibition in macrophages reduces ventricular arrhythmias in rats after myocardial ischemia-reperfusion.
Adv Clin Exp Med
; 30(4): 413-420, 2021 Apr.
Article
em En
| MEDLINE
| ID: mdl-33908199
ABSTRACT
BACKGROUND:
Myocardial ischemia-reperfusion (I/R) injury is still thought to be an unsolved puzzle that may lead to reperfusion arrhythmias and sudden cardiac death. Inflammation plays a key role in myocardial I/R. Studies have indicated that purinoceptor 2Y12 (P2Y12) antagonists have anti-inflammatory properties that are cardioprotective.OBJECTIVES:
In this study, we explored whether inhibition of P2Y12 in macrophages could reduce cardiac inflammation and attenuate reperfusion arrhythmias after myocardial I/R. MATERIAL ANDMETHODS:
Rats were randomly divided into 4 groups group A (control + vehicle); group B (control + P2Y12 shRNA lentiviral vector); group C (myocardial I/R + vehicle); and group D (myocardial I/R + P2Y12 shRNA lentiviral vector). Infarct size, reperfusion arrhythmias, and P2Y12 and platelet endothelial cell adhesion molecule-1 (CD31) protein expression were measured.RESULTS:
The incidence of reperfusion ventricular tachycardia and fibrillation (VT/VF) was 90% in the I/R group, while it was reduced to 50% by P2Y12 shRNA treatment. Ionized calcium binding adapter molecule 1 and P2Y12 immunoreactivity in the myocardial I/R + P2Y12 shRNA group was lower compared to the myocardial I/R group. P2Y12 shRNA treatment increased α-smooth muscle actin (α-SMA) and CD31 protein expression, as evidence by western blot and immunohistochemistry analyses (0.31 ±0.01 compared to 0.26 ±0.008, group D compared to group C, p < 0.05).CONCLUSIONS:
Inhibition of P2Y12 in macrophages improved reperfusion arrhythmias in our rat I/R model, suggesting that blocking P2Y12 could decrease the inflammatory response after cardiac perfusion.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão Miocárdica
Limite:
Animals
Idioma:
En
Revista:
Adv Clin Exp Med
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China