Peptides from Harpadon nehereus Bone Ameliorate Angiotensin II-Induced HUVEC Injury and Dysfunction through Activation of the AKT/eNOS and Nrf2 Pathway

[Image: see text] Angiotensin II (Ang II)-induced vascular endothelial cell injury and dysfunction are important pathophysiological factors in the occurrence and development of hypertension. In this study, the amelioration effects of two peptides KA-8 (KLHDEEVA) and PG-7 (PSRILYG) from Harpadon nehereus bone on Ang II-induced damage and dysfunction in human umbilical vein endothelial cells (HUVECs) were investigated. The results showed that they could significantly decrease the reactive oxygen species (ROS) level and increase the activity of antioxidant enzymes in Ang II-induced HUVEC. Two peptides, especially PG-7, significantly upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, PG-7 significantly reduced the level of expression of endothelin-1(ET-1) and increased the phosphorylation level of phosphoinositide 3-kinase (PI3K), serine/threonine kinase (AKT), and nitric oxide synthase (eNOS). These results indicated that the two peptides, especially PG-7, can ameliorate angiotensin II-induced HUVEC injury and dysfunction through activation of the AKT/eNOS and Nrf2 pathway. Furthermore, PG-7 showed a stronger affinity with angiotensin-converting enzyme (ACE) and ACE inhibitory than KA-8. In conclusion, peptide PG-7 reveals potential in the prevention and treatment of hypertension.