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      Impacto de la apolipoproteína A5 en el riesgo cardiovascular: Modulaciones genéticas y ambientales Translated title: Impact of apolipoprotein A5 on cardiovascular risk: Genetic and environmental modulation

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          Translated abstract

          Triglyceride concentrations are an independent risk factor for coronary heart disease. Apolipoprotein A5 gene (APOA5) has an important role determining triglyceride metabolism and it is a potential cardiovascular risk. However the mechanisms for these actions are not well-known. Despite the different allelic frequency of its major polymorphisms in different populations, multiple studies have shown consistent associations between these variants and fasting triglycerides. Variations in the APOA5 gene have also been associated with postprandial triglycerides, as well as with different sizes of lipoproteins and other markers. Moreover, some of the APOA5 gene variants have been associated with ischemic heart disease, stroke, and carotid intima media thickness, although the references on this issue are scanty and contradictory. This may be due to the presence of gene-environment interactions that have been poorly studied until now. Among the few studies that have examined the infuence of environmental factors on possible genetic variations, the most important are those that contemplate possible gene-diet interactions. However, the evidence is still scarce and more research is required in the feld of nutrigenomics. To understand the impact of this gene on cardiovascular disease, we review the genetic functionality and variability of APOA5, its associations with intermediate and fnal phenotypes and gene-environment interactions detected.

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          An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing.

          Comparison of genomic DNA sequences from human and mouse revealed a new apolipoprotein (APO) gene (APOAV) located proximal to the well-characterized APOAI/CIII/AIV gene cluster on human 11q23. Mice expressing a human APOAV transgene showed a decrease in plasma triglyceride concentrations to one-third of those in control mice; conversely, knockout mice lacking Apoav had four times as much plasma triglycerides as controls. In humans, single nucleotide polymorphisms (SNPs) across the APOAV locus were found to be significantly associated with plasma triglyceride levels in two independent studies. These findings indicate that APOAV is an important determinant of plasma triglyceride levels, a major risk factor for coronary artery disease.
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            Self-assembled magnetic matrices for DNA separation chips.

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              ApoAV reduces plasma triglycerides by inhibiting very low density lipoprotein-triglyceride (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis.

              ApoAV has been discovered recently as a novel modifier of triglyceride (TG) metabolism, but the pathways involved are currently unknown. To gain insight into the function of apoAV, adenovirus-mediated gene transfer of murine apoa5 to C57Bl/6 mice was employed. The injection of low doses of Ad-apoa5 (1-5 x 10(8) plaqueforming units/mouse) dose-dependently reduced plasma very low density lipoprotein (VLDL)-TG levels. First, we evaluated whether a reduced hepatic VLDL production contributed to the TG-lowering effect. Ad-apoa5 treatment dose-dependently diminished (29-37%) the VLDL-TG production rate without affecting VLDL particle production, suggesting that apoAV impairs the lipidation of apoB. Second, Ad-apoa5 treatment dose-dependently reduced (68-88%) the postprandial hypertriglyceridemia following an intragastric fat load, suggesting that apoAV also stimulates the lipoprotein lipase (LPL)-dependent clearance of TG-rich lipoproteins. Indeed, recombinant apoAV was found to dose-dependently stimulate LPL activity up to 2.3-fold in vitro. Accordingly, intravenously injected VLDL-like TG-rich emulsions were cleared at an accelerated rate concomitant with the increased uptake of emulsion TG-derived fatty acids by skeletal muscle and white adipose tissue in Ad-apoa5-treated mice. From these data, we conclude that apoAV is a potent stimulator of LPL activity. Thus, apoAV lowers plasma TG by both reducing the hepatic VLDL-TG production rate and by enhancing the lipolytic conversion of TG-rich lipoproteins.
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                Author and article information

                Journal
                rmc
                Revista médica de Chile
                Rev. méd. Chile
                Sociedad Médica de Santiago (Santiago, , Chile )
                0034-9887
                July 2010
                : 138
                : 7
                : 868-880
                Affiliations
                [02] orgnameInstituto de Salud Carlos III orgdiv1CIBER Fisiopatología de la Obesidad y Nutrición España
                [01] orgnameUniversitat de València orgdiv1Departamento de Medicina Preventiva y Salud Pública orgdiv2Ciencias de la Alimentación, Toxicología y Medicina Legal España
                Article
                S0034-98872010000700013 S0034-9887(10)13800713
                10.4067/S0034-98872010000700013
                fa5988a7-2043-4f45-a567-adeb435fd684

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 08 June 2009
                : 11 December 2009
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 66, Pages: 13
                Product

                SciELO Chile

                Categories
                ARTICULOS DE REVISION

                APOA5 protein human,Coronary disease,Triglycerides
                APOA5 protein human, Coronary disease, Triglycerides

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