Protocatechuic aldehyde inhibits lipopolysaccharide-induced human umbilical vein endothelial cell apoptosis via regulation of caspase-3.

Apoptosis of vascular endothelial cells results in the loss of endothelial integrity, and is a risk factor of atherosclerosis (AS). Lipopolysaccharide (LPS) stimulates inflammation during AS. The current study examined the effect of a potent water-soluble antioxidant, protocatechuic aldehyde (PCA; derived from the Chinese herb Salvia miltiorrhiza) on apoptosis in human umbilical vein endothelial cells (HUVECs) stimulated with LPS. The LPS (15 µg/ml) stimulation for 30 h resulted in significant HUVEC apoptosis, as detected by Hoechst 33258 staining and Annexin V analysis. The PCA (0.25-1.0 mmol/L, 12 h) inhibited LPS-induced HUVEC apoptosis in a dose-dependent manner. Lipopolysaccharide induced caspase-3 activation, but had no significant effect on caspase-2, Bcl-2/Bax, cytochrome c, caspase-9 and granzyme B expression. Protocatechuic aldehyde (0.25-1.0 mmol/L) significantly inhibited caspase-3 activation in a dose-dependent manner. A specific caspase-3 inhibitor also protected against LPS-induced apoptosis; however, no cooperative effect of PCA and the inhibitor was observed in this study. Collectively, these results indicate that PCA inhibits LPS-induced apoptosis in HUVECs through a mechanism that involves caspase-3.