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      Protective effect of Xin Mai Jia ultrafiltration extract on human umbilical vein endothelial cell injury induced by hydrogen peroxide and the effect on the NO-cGMP signaling pathway

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          Abstract

          The aim of the present study was to evaluate the protective effect of the ultrafiltration extract of Xin Mai Jia (XMJ) on a human umbilical vein endothelial cell (HUVEC) injury model induced by hydrogen peroxide (H 2O 2), by providing experimental data to investigate the mechanism and efficacy underlying the therapeutic effects on atherosclerosis. HUVECs were first injured by H 2O 2 and then varying final concentrations of the Chinese herb extract were added. Effects of the XMJ extract on morphology, activity, monolayer permeability, biochemical indicators, cytokines, endothelial nitric oxide synthase (eNOS) protein content and eNOS gene expression in the HUVECs were analyzed. H 2O 2 significantly promoted HUVEC injury. The XMJ ultrafiltration extract significantly improved the morphological changes in the injured HUVECs. In addition, XMJ treatment increased cell activity and decreased monolayer permeability. The expression levels of intracellular adhesion molecule-1, vascular adhesion molecule-1, interleukin-1 and -6 and nuclear factor-κB decreased, while the expression levels of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 increased with XMJ administration. Increased levels of nitric oxide (NO), eNOS protein and eNOS gene expression were also observed. Therefore, the XMJ ultrafiltration extract exhibits marked anti-inflammatory effects and antioxidant abilities. These properties significantly inhibited the H 2O 2-induced injury of HUVECs, which may be associated with the NO-cyclic guanosine monophosphate signaling pathway.

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          Expression of multiple isoforms of nitric oxide synthase in normal and atherosclerotic vessels.

          Atherosclerosis is associated with reduced endothelium-derived relaxing factor bioactivity. To determine whether this is due to decreased synthesis of nitric oxide synthase (NOS), we examined normal and atherosclerotic human vessels by in situ hybridization and immunocytochemistry by using probes specific for endothelial (ecNOS), inducible (iNOS), and neuronal (nNOS) NOS isoforms, ecNOS was detected in endothelial cells overlying normal human aortas, fatty streaks, and advanced atherosclerotic lesions. A comparison of the relative expression of ecNOS to von Willebrand factor on serial sections of normal and atherosclerotic vessels indicated that there was a decrease in the number of endothelial cells expressing ecNOS in advanced lesions. iNOS and nNOS were not detected in normal vessels, but widespread production of these isoforms was found in early and advanced lesions associated with macrophages, endothelial cells, and mesenchymal-appearing intimal cells. These data suggest that there is (1) a loss of ecNOS expression by endothelial cells over advanced atherosclerotic lesions and (2) a significant increase in overall NOS synthesis by other cell types in advanced lesions composed of the ecNOS, nNOS, and iNOS isoforms. We hypothesize that the increased expression of NOS and presumably NO in atherosclerotic plaques may be related to cell death and necrosis in these tissues.
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            Recombinant HDL(Milano) exerts greater anti-inflammatory and plaque stabilizing properties than HDL(wild-type).

            The aim of this study was to compare the effects of HDL(Milano) and HDL(wild-type), on regression and stabilization of atherosclerosis. Atherosclerotic New Zealand White rabbits received 2 infusions, 4 days apart, of HDL(Milano) (75mg/kg of apoA-I(Milano)), HDL(wild-type) (75mg/kg apoA-I(wild-type)) or placebo. Pre- and post-treatment plaque volume was assessed by MRI. Markers of plaque vulnerability and inflammation were evaluated. Liver and aortic cholesterol content, aortic ABCA-1 and liver SR-BI were quantified. The effect of apoA-I Milano and wild-type proteins on MCP-1 and COX-2 expression by macrophages was evaluated in vitro. Both forms of HDL induced aortic plaque regression (-4.1% and -2.6% vs. pre-treatment in HDL(Milano) and HDL(wild-type) respectively, p<0.001 and p=0.009). A similar reduction in cholesterol content of aorta and liver was observed with both treatments vs. placebo. The expression of aortic ABCA-1 and hepatic SR-BI was significantly higher in both treated groups vs. placebo. A significantly reduced plaque macrophage density was observed in the HDL(Milano) vs. both HDL(wild-type) and placebo groups. Plaque levels of COX-2, MCP-1, Caspase-3 antigen and MMP-2 activity were significantly reduced in the HDL(Milano) vs. both HDL(wild-type) and placebo groups. In vitro studies showed that apoA-I(Milano) protein significantly reduced expression of COX-2 and MCP-1 in oxLDL loaded macrophages vs. apoA-I(wild-type). Despite a similar effect on acute plaque regression, the infusion of HDL(Milano) exerts superior anti-inflammatory and plaque stabilizing effects than HDL(wild-type) in the short term. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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              Red grape seed extract improves lipid profiles and decreases oxidized low-density lipoprotein in patients with mild hyperlipidemia.

              Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress induction that leads to the formation of atherosclerotic plaque. Oxidized low-density lipoprotein particles (Ox-LDL) have a key role in the pathogenesis of atherosclerosis. The lipid-lowering properties and antioxidants of the grape seed can be beneficial in atherosclerosis prevention. We conducted a randomized double-blind placebo-controlled crossover clinical trial. Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape seed extract (RGSE) or placebo for 8 weeks. After an 8-week washout period, the groups were crossed over for another 8 weeks. Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase. RGSE consumption reduced total cholesterol (-10.68±26.76 mg/dL, P=.015), LDL cholesterol (-9.66±23.92 mg/dL, P=.014), and Ox-LDL (-5.47±12.12 mg/dL, P=.008). While triglyceride and very low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased by RGSE, the changes were not statistically significant. RGSE consumption decreases Ox-LDL and has beneficial effects on lipid profile-consequently decreasing the risk of atherosclerosis and cardiovascular disorders-in mild hyperlipidemic individuals.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                July 2014
                02 May 2014
                02 May 2014
                : 8
                : 1
                : 38-48
                Affiliations
                [1 ]School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
                [2 ]Department of Nephrology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
                [3 ]College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
                [4 ]Department of Inspection, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
                [5 ]Modern Technology Education Center, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
                Author notes
                Correspondence to: Professor Guangrui Wan, Modern Technology Education Center, Xinxiang Medical University, 45 Dongduan Wuyi Road, Xinxiang, Henan 453003, P.R. China, E-mail: guangruiw@ 123456126.com
                [*]

                Contributed equally

                Article
                etm-08-01-0038
                10.3892/etm.2014.1700
                4061210
                24944594
                311445e2-8f52-403c-8418-350d5a5523f6
                Copyright © 2014, Spandidos Publications

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                : 01 December 2013
                : 25 March 2014
                Categories
                Articles

                Medicine
                xin mai jia,human umbilical vein endothelial cell,hydrogen peroxide,atherosclerosis
                Medicine
                xin mai jia, human umbilical vein endothelial cell, hydrogen peroxide, atherosclerosis

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