4-hydroxy-2-nonenal decreases coronary endothelial cell migration: Potentiation by aldehyde dehydrogenase 2...

4-hydroxynonenal (4HNE) is a reactive aldehyde, which is involved in oxidative stress associated pathogenesis. The cellular toxicity of 4HNE is mitigated by aldehyde dehydrogenase (ALDH) 2. Thus, we hypothesize that ALDH2 inhibition exacerbates 4HNE-induced decrease in coronary endothelial cell (EC) migration in vitro. To test our hypothesis, we pharmacologically inhibited ALDH2 in cultured mouse coronary ECs (MCECs) by disulfiram (DSF) (2.5 μM) before challenging the cells with different doses of 4HNE (25, 50 and 75 μM) for 4, 12, 16 and 24 h. We evaluated MCEC migration by scratch wound migration assay. 4HNE attenuated MCEC migration significantly relative to control (P < .05), which was exacerbated with DSF pretreatment (P < .05). DSF pretreatment exacerbated 4HNE-induced decrease in ALDH2 activity in MCECs. Next, we showed that 75 μM 4HNE significantly decreased the intracellular mRNA levels of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), focal adhesion kinase (FAK) and other promigratory genes compared to control, which were further decreased by DSF pretreatment. 75 μM 4HNE also decreased the protein levels of VEGFR2, FAK, phospho-FAK, Src and paxillin in MCECs. Thus, we conclude that ALDH2 inhibition potentiates 4HNE-induced decrease in MCECs migration in vitro.