Abstract
Coronary microembolization (CME) is a common complication of percutaneous coronary intervention (PCI) for acute coronary syndrome. It leads to myocardial apoptosis and cardiac dysfunction. Nicorandil pretreatment can prevent PCI-related myocardial injury and reduce the incidence of no- or slow-reflow phenomena. This cardioprotective effect is probably attributable to the suppression of CME-induced cardiomyocyte apoptosis, but the specific mechanisms have not been clarified. We aimed to investigate the protective effects of nicorandil pretreatment on CME-induced myocardial injury and clarify the underlying mechanisms. In vivo studies, we used echocardiography, cardiac-enzymes measurement, hematoxylin–basic fuchsin–picric acid staining, TUNEL assay, and western blot, and found that CME significantly increased apoptotic cardiomyocytes in the infarct and peri-infarct areas in rats. The PI3K/Akt signaling pathway was involved in cardiomyocyte apoptosis. Nicorandil pretreatment given 7 days before CME effectively reduced cardiomyocyte apoptosis and myocardial injuries in rats, mainly through the activation of PI3K/Akt signaling. In vitro studies further showed that nicorandil reduced hypoxia-induced cardiomyocyte apoptosis and improved cardiomyocyte-survival rate. The PI3K-specific inhibitor LY294002 reduced these cardioprotective effects, indicating that they were attributable to the activation of the PI3K/Akt signaling pathway. In conclusion, nicorandil has significant cardioprotective effects in CME mainly through the activation of the PI3K/Akt signaling pathway and reduction of CME-induced cardiomyocyte apoptosis. Our findings may provide important support for the pre-PCI use of nicorandil to reduce post-PCI myocardial injuries.
Highlights
Coronary microembolization (CME) is an intractable complication of percutaneous coronary intervention (PCI) for acute coronary syndrome
This study aimed to determine the effects of nicorandil pretreatment on hypoxia-induced cardiomyocyte apoptosis and the PI3K/Akt signaling pathway in rats and in vitro, in order to uncover the mechanisms underlying the cardioprotective effects of nicorandil in CME
Pretreatment with LY294002 alone exacerbated cardiomyocyte apoptosis, as indicated by significant downregulation of p-PI3K and p-Akt expression, and the Bcl-2/Bax ratio and significant upregulation of cleaved caspase-3 expression. These results showed that the PI3K/Akt signaling pathway is involved in hypoxia-induced cardiomyocyte apoptosis, and that nicorandil pretreatment can alleviate this apoptosis through regulating the PI3K/Akt signaling pathway
Summary
Coronary microembolization (CME) is an intractable complication of percutaneous coronary intervention (PCI) for acute coronary syndrome. It occurs when atherosclerotic plaques detach and obstruct the distal microvessels, resulting in no- or slow-reflow phenomena. The downregulation of PTEN gene expression significantly alleviates cardiomyocyte apoptosis and improves cardiac contractility mainly through the www.impactjournals.com/oncotarget activation of the PI3K/Akt signaling pathway. Drugs such as atorvastatin, which upregulate the PI3K/Akt signaling pathway, can effectively reduce CME-induced cardiomyocyte apoptosis and the subsequent myocardial injuries
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