Antiarrhythmogenic Effect of Reconstituted High-Density Lipoprotein Against Ischemia/Reperfusion in Rats

Antiarrhythmogenic Effect of Reconstituted High-Density Lipoprotein Against Ischemia/Reperfusion in Rats Satoshi Imaizumi, Shin-ichiro Miura, Kazuto Nakamura, Yoshihiro Kiya, Yoshinari Uehara, Bo Zhang, Yoshino Matsuo, Hidenori Urata, Munehito Ideishi, Kerry-Anne Rye, Masataka Sata, Keijiro Saku We analyzed the suppression of reperfusion-induced arrhythmias by reconstituted high-density lipoprotein (rHDL) in rats. Ventricular arrhythmias after reperfusion in rHDL–pre-treated rats were significantly suppressed. This effect was mediated by an Akt protein kinase/extracellular-signal-regulated kinase (ERK)/endothelial nitric oxide (NO) synthesis pathway. We also found that rHDL activated Akt/ERK/NO in human coronary artery endothelial cells. In addition, rHDL activated ERK in adenosine triphosphate-binding cassette transporter A1- or G1-transfected but not scavenger receptor class B, type I–transfected ldlA7 cells. Therefore, rHDL-induced NO production, probably through an Akt/ERK/NO pathway in endothelial cells, may induce an antiarrhythmogenic effect. The HDL-based therapy may hold the promise of reducing the incidence of such arrhythmias after ischemia/reperfusion.