In Vitro Vascular-Protective Effects of a Tilapia By-Product Oligopeptide on Angiotensin II-Induced Hypertensive Endothelial Injury in HUVEC by Nrf2/NF-κB Pathways.

Jiali Chen,Zhong-Ji Qian,Shengli Sun,Pengzhi Hong,Mei-Fang Chen,Chunxia Zhou,Chengyong Li,Fang Gong

doi:10.3390/md17070431

Jiali Chen, Zhong-Ji Qian + Show 6 more

Open Access

https://doi.org/10.3390/md17070431

Copy DOI

Journal: Marine Drugs	Publication Date: Jul 23, 2019
Citations: 17	License type: CC BY 4.0

Affiliation: Guangdong Ocean University

Abstract

Angiotensin II (Ang II) is closely involved in endothelial injury during the development of hypertension. In this study, the protective effects of the tilapia by-product oligopeptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) on oxidative stress and endothelial injury in Angiotensin II (Ang II)-stimulated human umbilical vein endothelial cells (HUVEC) were evaluated. LSGYGP dose-dependently suppressed the fluorescence intensities of nitric oxide (NO) and reactive oxygen species (ROS), inhibited the nuclear factor-kappa B (NF-κB) pathway, and reduced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and endothelin-1 (ET-1) expression, as shown by western blot. In addition, it attenuated the expression of gamma-glutamyltransferase (GGT) and heme oxygenase 1 (HO-1), as well as increasing superoxide dismutase (SOD) and glutathione (GSH) expression through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Other experiments revealed that LSGYGP increased the apoptotic inhibition ratio between cleaved-caspase-3/procaspase-3, reduced expressions of pro-apoptotic ratio between Bcl-2/Bax, inhibited phosphorylation of mitogen-activated protein kinases (MAPK), and increased phosphorylation of the serine/threonine kinase (Akt) pathway. Furthermore, LSGYGP significantly decreased Ang II-induced DNA damage in a comet assay, and molecular docking results showed that the steady interaction between LSGYGP with NF-κB may be attributed to hydrogen bonds. These results suggest that this oligopeptide is effective in protecting against Ang II-induced HUVEC injury through the reduction of oxidative stress and alleviating endothelial damage. Thus, it has the potential for the therapeutic treatment of hypertension-associated diseases.

Highlights

IntroductionEndothelial dysfunction is regarded as a predictor of cardiovascular diseases (CVD) and long-term clinical outcomes, such as heart disease, arteriosclerosis, stroke, kidney disease, and hypertension
Endothelial dysfunction is regarded as a predictor of cardiovascular diseases (CVD) and long-term clinical outcomes, such as heart disease, arteriosclerosis, stroke, kidney disease, and hypertension.Hypertension is a CVD which results in high death rates; its pathogenesis and precise mechanism, at present, remain unknown
Viability, and LSGYGP treatment showed a cytoprotective effect on Angiotensin II (Ang II)-stimulated human umbilical vein endothelial cells (HUVEC) in a

Summary

Introduction

Endothelial dysfunction is regarded as a predictor of cardiovascular diseases (CVD) and long-term clinical outcomes, such as heart disease, arteriosclerosis, stroke, kidney disease, and hypertension. Hypertension is a CVD which results in high death rates; its pathogenesis and precise mechanism, at present, remain unknown. There is a common perception that hypertension is connected with vascular endothelial dysfunction caused by inflammation cytokines and oxidative stress in vascular endothelial cells [1,2]. Research has shown that inflammatory stimulation in endothelial cells could be induced by the extracellular stimulators angiotensin II (Ang II) [3], tumor necrosis factor-alpha. Mar. Drugs 2019, 17, 431; doi:10.3390/md17070431 www.mdpi.com/journal/marinedrugs.

Objectives

Methods

Results

Conclusion