P2Y12 inhibition in macrophages reduces ventricular arrhythmias in rats after myocardial ischemia-reperfusion.

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. In this study, we explored whether inhibition of P2Y12 in macrophages could reduce cardiac inflammation and attenuate reperfusion arrhythmias after myocardial I/R. 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. 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). 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.

Citation

Lu Wang, Na Li, Fei Wang, Lianqun Cui. P2Y12 inhibition in macrophages reduces ventricular arrhythmias in rats after myocardial ischemia-reperfusion. Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2021 Apr;30(4):413-420

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PMID: 33908199

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