Abstract
BackgroundAtherosclerosis 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).MethodsAfter 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.ResultsInitially, 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.ConclusionsThese results suggest that Klotho has a potential therapeutic effect on attenuating endothelial dysfunction and ameliorating atherosclerosis.
Highlights
Atherosclerosis is a common cardiovascular disease that causes myocardial infarction, heart failure, and stroke
Klotho prevented the cytotoxic activity of oxidized low density lipoprotein (ox-low density lipoprotein (LDL)) in human umbilical vein endothelial cells (HUVECs) As described above, ox-LDL may injurethe vascular endothelium through multiple pathways
We observed cellular morphology (Fig. 1a) and measured viability by MTT assay (Fig. 1b) in HUVECs after treatment with different concentrations (25–200 μg/ml) of ox-LDL to reveal the activity of ox-LDL under an optical microscope (Fig. 1a), we found that HUVECs were polygon or displayed short fusiform and were arranged as pebbles
Summary
Atherosclerosis is a common cardiovascular disease that causes myocardial infarction, heart failure, and stroke. Atherosclerosis is a common arterial disorder caused by a buildup of plaque. Fat and cholesterol gather in the arteries to form the plaque. Plaque rupture causes blood clots that block coronary arteries resulting in a heart attack and obstruction of cerebrovascular vessels (stroke) [1]. Increased low density lipoprotein (LDL) and its oxidative form, oxidized low density lipoprotein (ox-LDL), inthe vascular subendothelium is characteristic of atherogenesis. These molecules attract and activate inflammatory cells, such as monocytes, T cells and macrophages. The activated macrophages thereupon release pro-inflammatory cytokines, reactive oxygen species (ROS), and proteolytic enzymes resulting in matrix degradation and atherosclerotic
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