Protective effects of phosphocreatine on human vascular endothelial cells against hydrogen peroxide-induced apoptosis and in the hyperlipidemic rat model.

Phosphocreatine (PCr) has been shown to have a cardio-protective effect during cardiopulmonary resuscitation (CPR). However, little is known about its impact on atherosclerosis. In this study, we first evaluated the pharmacological effects of PCr on antioxidative defenses and mitochondrial protection against hydrogen peroxide (H 2 O 2) induced human umbilical vascular endothelial cells (HUVECs) damage. Then we investigated the hypolipidemic and antioxidative effects of PCr on hyperlipidemic rat model. Via in vitro studies, H 2 O 2 significantly reduced cell viability and increased apoptosis rate of HUVECs, while pretreatment with PCr abolished its apoptotic effect. PCr could reduce the generation of ROS induced by H 2 O 2. Moreover, PCr could increase the activity of SOD and the content of NO, as well as decrease the activity of LDH and the content of MDA. PCr could also antagonize H 2 O 2 -induced up-regulation of Bax, cleaved-caspase3, cleaved-caspase9, and H 2 O 2 -induced down-regulation of Bcl-2 and p-Akt/Akt ratio. In addition, PCr reduced U937 cells' adhesion to H 2 O 2 -stimulated HUVECs. Via in vivo study, PCr could decrease MDA, TC, TG and LDL-C levels in hyperlipidemic rats. Finally, different-concentration PCr could increase the leaching of TC, HDL, and TG from fresh human atherosclerotic plaques. In conclusion, PCr could suppress H 2 O 2 -induced apoptosis in HUVECs and reduce hyperlipidemia through inhibiting ROS generation and modulating dysfunctional mitochondrial system, which might be an effective new therapeutic strategy to further prevent atherosclerosis. [Display omitted] • Phosphocreatine (PCr) could reduce H 2 O 2 -induced ROS overexpression by modulating the PI3K/Akt signaling in HUVECs. • PCr could prevent H 2 O 2 -induced apoptosis of HUVECs through regulating caspase activation in mitochondrial system. • PCr could control hypercholesterolemia by reducing cell adhesion, improving lipid profile and modulating oxidative stress. • PCr may provide a novel therapeutic avenue for the treatment of atherosclerosis and new cellular protective mechanisms. [ABSTRACT FROM AUTHOR]