DPO-1, a specific inhibitor of Kv1.5, significantly reduced H2O2-induced endothelial cell apoptosis from 24% to 14% in an in vivo rat carotid arterial model.
Does Kv1.5 inhibition reduce oxidative stress-induced vascular endothelial cell apoptosis and ROS production in preclinical models?
Inhibition of the Kv1.5 potassium channel attenuates oxidative stress-induced vascular endothelial cell apoptosis, suggesting it may be a potential therapeutic target for vascular injury.
Absolute Event Rate: 14% vs 24%
p-value: p=<0.01
Endothelial injury related to oxidative stress is a key event in cardiovascular diseases, such as hypertension and atherosclerosis. The activation of the redox-sensitive Kv1.5 potassium channel mediates mitochondrial reactive oxygen species (ROS)-induced apoptosis in vascular smooth muscle cells and some cancer cells. Kv1.5 channel is therefore taken as a new potential therapeutic target for pulmonary hypertension and cancers. Although Kv1.5 is abundantly expressed in vascular endothelium, there is little knowledge of its role in endothelial injury related to oxidative stress. We found that DPO-1, a specific inhibitor of Kv1.5, attenuated H(2)O(2)-evoked endothelial cell apoptosis in an in vivo rat carotid arterial model. In human umbilical vein endothelial cells (HUVECs) and human pulmonary arterial endothelial cells (HPAECs), angiotensin II and oxLDL time- or concentration-dependently enhanced Kv1.5 protein expression in parallel with the production of intracellular ROS and endothelial cell injury. Moreover, siRNA-mediated knockdown of Kv1.5 attenuated, whereas adenovirus-mediated Kv1.5 cDNA overexpression enhanced oxLDL-induced cellular damage, NADPH oxidase and mitochondria-derived ROS production and restored the decrease in protein expression of mitochondria uncoupling protein 2 (UCP2). Collectively, these data suggest that Kv1.5 may play an important role in oxidative vascular endothelial injury.
Chen et al. (Wed,) conducted a other in Oxidative vascular endothelial cell injury (n=18). DPO-1 (Kv1.5 inhibitor) vs. H2O2 injury without DPO-1 was evaluated on Endothelial cell apoptosis (p=<0.01). DPO-1, a specific inhibitor of Kv1.5, significantly reduced H2O2-induced endothelial cell apoptosis from 24% to 14% in an in vivo rat carotid arterial model.