A0625 Cinnameldehyde Attenuated Endothelial Dysfunction through Nrf2 Activation as a TRPA1 Agonist

Objectives: Advancing age is characterized with the development of vascular endothelial dysfunction which is the major risk factor for the development of cardiovascular diseases. TRPA1 is involved in lifespan and its agonist cinnameldehyde(CA)mediates endothelial vasorelaxation. Therefore, we hypothesized that TRPA1 is involved in aging-related endothelial dysfunction and CA administration would improve endothelial function. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured until 14th passage and the 6th passage were used as control. Twenty-four months-old male Sprague Dawley (SD) rats were given dietary CA (0.2%) and six months-old rodents were used as young control. Rodent carotid arteries vasorelaxation was detected by wire myograph. TRPA1, Nrf2, UCP2 and its target genes as well as eNOS, p-eNOS were analysed by immunoblotting. Results: Immunoblotting and immunofluorescence confirmed the TRPA1 expression in HUVECs and vascular endothelium. CA(10 μM) promoted Nrf2 nuclear translocation and eNOS phosphorylation, led to the up-regulation of HO-1, GPx-1, NQO-1 and a reduction in ROS production in HUVECs. However, these effects of CA could be reversed by TRPA1 antagonist, HC030031 (10 μM), Nrf2 inhibitor brusatol (40 nM) or UCP2 inhibitor. NO level was found decreased, and enthdothelium dependent relaxation was impaired in carotid arteries of aged rats, but both improved after 12 weeks of CA administration. Immunoblotting showed the expression of TRAP1, Nrf2, UCP2 and p-eNOS significantly decreased in vascular tissue of aged rats but partly restored after CA treatment. Conclusion: TRPA1 may be involved in aging related endothelial dysfunction and CA improved endothelial dependent vasorelaxation through Nrf2 activation as a TRPA1 agonist.