| Endothelial dysfunction is critical pathogenic factor in the development of cardiovascular diseases such as atherosclerosis, hypercholesteremia and disseminated intravascular coagulation. Oxidative stress and inflammation play critical roles in endothelial dysfunction.Prostaglandin E1 (PGE1), which is an important member of the prostaglandins family, is a product of arachidonic acid metabolism by cycloxygenase. PGE1 has vasodilator effects on the systemic and pulmonary circulation and cardio-protective effects during ischemia and reoxygenation. In addition, beneficial effects on angiogenesis, platelet aggregation, blood viscosity and fibrinolysis have been observed. Moreover, increasing attention has now been paid to the anti-oxidant activity, anti-inflammation activity and cytoprotective action of PGE1. PGE1 protected human retinal pigment epithelial cells against oxidative injury; prevented the production of ROS in the intestinal mucosa of methotrexate-treated rats; reduced circulating soluble adhesion molecules in peripheral vascular disease, peripheral arterial obstructive disease and hepatic ischemia/reperfusion injury. However, no direct evidence was provided about the protective effects of PGE1 on damaged vascular endothelium, which is an important contributor to the development of cardiovascular diseases.This study, therefore, was conducted to examine the protective effect of PGE1 on human umbilical vein endothelial cells (HUVECs) injured by hydrogen peroxide (H2O2) or tumor necrosis factor-a (TNF-a), and explore its mechanisms.We firstly examined the protective effect of PGE1 on HUVECs injured by H2O2, and find:(1) H2O2 (200uM) markedly increased cell permeability, damaged cellular antioxidant defenses and furthermore induced endothelial cell apoptosis. (2) PGE1 (0.25,0.50,1.00uM) dose-dependently increased cell viability and attenuated LDH release in H2O2-injuried HUVECs. (3) PGE1 (0.25,0.50,1.00uM) significantly reduced intracellular MDA, increased intracellular SOD and GSH-Pox activity, and reduced intracellular ROS in H2O2-injuried HUVECs. (4) PGE, (0.25,0.50, 1.00uM) significantly reduced apoptotic rate induced by H2O2 in a concentration-dependent manner. (5)PGE1 (0.25,0.50, 1.00uM) triggered NO release, eons protein and mRNA expression a dose-dependent manner in H2O2-injuried HUVEC. As stated above, we concluded that PGE1 significantly protected HUVECs from H2O2-induced cell damage, which was possibly mediated at least in part by a mechanism linked to the up-regulation of NO expression. Therefore, PGE1 inhibited vascular oxidative stress and further prevented the development of endothelial dysfunction.Then we examined the protective effect of PGE1 on HUVECs injured by TNF-a, and find:(1) TNF-a (lOng/ml) significantly increased VCAM-1, ICAM-1 and E-selectin expression, increased THP-1 cell adhesion to HUVECs. (2) PGE] (0.25, 0.50,1.00uM) significantly reduced the increased protein and mRNA expression of VCAM-1, ICAM-1 and E-selectin in TNF-a-treated HUVECs. (3) PGE, inhibits THP-1 cell adhesion to TNF-a-treated HUVECs. (4) PGE, (0.25,0.50,1.00uM) significantly reduced the increased intracellular ROS induced by TNF-a in TNF-a-treated HUVECs. (4) PGE1 (0.25,0.5, 1.0uM) decreased the level of p65 in the nucleus and increased p65 in the cytoplasm in TNF-a-treated HUVECs. In other word, PGE1 inhibited nuclear translocation of p65 in TNF-a-treated HUVECs. In summary, the present data suggested that PGE1 suppressed TNF-a-induced vascular inflammation which was possibly mediated by inhibition of oxidative stress and NF-kB activation. Therefore, PGE1 inhibited vascular inflammation and further prevented the development of endothelial dysfunction.In conclusion, PGE1 protected HUVECs from H2O2 or TNF-a induced injury, which shed light on the pharmacological basis for the clinical application of PGE1 for treatment of atherosclerosis and acute coronary syndrome, which are relevant to endothelial cell death.
|
PDF Full Text Request