Klotho ameliorates oxidized low density lipoprotein (ox-LDL)-induced oxidative stress via regulating LOX-1 and PI3K/Akt/eNOS pathways

• Published in: Lipids in health and disease 2017-04, Vol.16 (1), p.77-77, Article 77
• Main Authors: Yao, Yansheng, Wang, Yanbing, Zhang, Yibo, Liu, Chang
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Aging; AKT protein; Apoptosis; Arteriosclerosis; Atherogenesis; Atherosclerosis; Atherosclerosis - metabolism; Atherosclerosis - pathology; Calcification; Cardiovascular disease; Cell adhesion & migration; Cell growth; Cell Survival; Cells, Cultured; Cerebral infarction; Cytokines; Diabetes; Endothelial cells; Endothelium; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Glucuronidase - genetics; Glucuronidase - metabolism; Heart diseases; Human umbilical vein endothelial cells; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - enzymology; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Inositol; Klotho; Klotho protein; Lectin-like ox-LDL receptor; Lipid Peroxidation; Lipoproteins, LDL - antagonists & inhibitors; Lipoproteins, LDL - metabolism; Low density lipoprotein; LOX-1 protein; Lysates; Malondialdehyde; Malondialdehyde - agonists; Malondialdehyde - antagonists & inhibitors; Malondialdehyde - metabolism; Myocardial infarction; Nitric oxide; Nitric Oxide - agonists; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - chemistry; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Nitric-oxide synthase; Oxidative Stress; Oxidized low density lipoprotein; Phosphatidylinositol 3-Kinase - antagonists & inhibitors; Phosphatidylinositol 3-Kinase - chemistry; Phosphatidylinositol 3-Kinase - genetics; Phosphatidylinositol 3-Kinase - metabolism; Polymerase chain reaction; Proteins; Proto-Oncogene Proteins c-akt - agonists; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Reactive oxygen species; Reactive Oxygen Species - agonists; Reactive Oxygen Species - antagonists & inhibitors; Reactive Oxygen Species - metabolism; Recombinant Proteins - metabolism; Scavenger Receptors, Class E - agonists; Scavenger Receptors, Class E - antagonists & inhibitors; Scavenger Receptors, Class E - metabolism; Second Messenger Systems; Stroke; Superoxide dismutase; Superoxide Dismutase - antagonists & inhibitors; Superoxide Dismutase - chemistry; Superoxide Dismutase - metabolism; Tumor necrosis factor-TNF; Umbilical vein
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/s12944-017-0447-0

Atherosclerosis is a common cardiovascular disease that causes myocardial infarction, heart failure, and stroke. Increased oxidized low density lipoprotein (ox-LDL) in the sub-endothelium is the characteristic origin of atherogenesis. Klotho, an anti-aging protein, has been reported to protect against atherosclerosis and ameliorate endothelial dysfunction in vivo. The aim of this study is to investigatethe anti-oxidative activity of Klothoin ox-LDL-treated human umbilical vein endothelial cells (HUVECs). After pre-treatment with 200 pMKlotho for 1 h, HUVECs were stimulated with 50 μg/ml ox-LDL for 24 h. Reactive oxygen species (ROS) and superoxide dismutase (SOD) levels were analyzed in the cells. Nitric oxide (NO) concertation was measured in the medium supernatant. Related proteins or genes were detected with Western blot or real time PCR, respectively, in the cell lysates. Initially, oxidative damage in HUVECs was established by adding 50 μg/mL ox-LDL, which resulted in decreased cellular viability, SOD/Cu/Zn-SOD and endothelial NO synthase (eNOS) expression and NO production, as well as increased malondialdehyde (MDA) levels, ROS production, inducible NO synthase (iNOS), phosphatidyl inositol-3 kinase (PI3K), protein kinase B (Akt), gp91 phox, and lectin-like ox-LDL receptor (LOX-1) expression in HUVECs. Pre-incubation with recombinant Klotho (200 pM) significantly prevented all of these alterations. These results suggest that Klotho can attenuate ox-LDL-induced oxidative stress in HUVECs through upregulating oxidative scavengers (SOD and NO) viaactivating the PI3K/Akt/eNOS pathway and depressing LOX-1expression. These results suggest that Klotho has a potential therapeutic effect on attenuating endothelial dysfunction and ameliorating atherosclerosis.