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M-011 TANSHINONE IIA ATTENUATES H2O2-INDUCED INJURY IN HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS

Background The injury of endothelial cell is the critical event of hypertension. In endothelial cell, oxidative stress is regarded as critical pathogenic factors in endothelial cell injury and apoptosis. Tanshinone IIA is the main effective component of Salvia miltiorrhiza known as ’Danshen’ in traditional Chinese medicine for treating cardiovascular disorders, but the mechanism by which it exerts the protective effect is not well established. The present study was designed to test the hypothesis whether tanshinone IIA can inhibit H2O2-induced injury in human umbilical vein endothelial cells. Methods Human umbilical vein endothelial cells (HUVECs) were treated with tanshinone IIA in the presence/absence of hydrogen peroxide (H2O2). The protective effects of tanshinone IIA against H2O2 were evaluated. Results HUVECs incubated with 200 &mgr;M H2O2 had significantly decreased the viability of endothelial cells, which was accompanied with apparent cells apoptosis, the activation of caspase-3 and the upregulation of p53 expression. However, pretreatment with tanshinone IIA(3–10 &mgr;M) resulted in a significant recovery from H2O2-induced cell apoptosis. Furthermore, pretreatment with tanshinone IIA decreased the activity of caspase-3 and p53 expression, which was known to play a key role in H2O2-induced cell apoptosis. Tanshinone IIA also induced activating transcription factor (ATF) 3 at both mRNA and protein level; while knockdown of ATF3 with ATF3 siRNA significantly reduced ATF3 protein levels and tanshinone IIA's protective effect. Conclusions The present study shows that tanshinone IIA can protect endothelial cells against oxidative injury induced by H2O2, suggesting that this compound may constitute a promising intervention against cardiovascular disorders and ATF3 may play an important role in this process.