Alteraciones en el contenido proteico y disfunción de lipoproteínas de alta densidad en ratones hiperhomocisteinémicos / Alterations in the protein content and dysfunction of high-density lipoproteins from hyperhomocysteinemic mice

OBJETIVOS: El objetivo de este estudio fue evaluar las alteraciones proteicas de las lipoproteínas de alta densidad (HDL) provocadas por la hiperhomocisteinemia inducida por ingesta de metionina en ratones y su relación con 2 de las propiedades antiaterogénicas más importantes de las HDL. Métodos y resultados La hiperhomocisteinemia inducida por administración de metionina resultó en un aumento (∼ 8 veces) de la concentración plasmática de homocisteína. La hiperhomocisteinemia se correlacionó inversamente con la concentración plasmática de colesterol HDL y del componente proteico principal de las HDL, la apolipoproteína (apo) A- I . El eflujo de colesterol desde macrófagos a las HDL in vivo disminuyó en ratones hiperhomocisteinémicos en comparación con los controles. Sin embargo, el transporte reverso del colesterol desde macrófagos a heces no se observó alterado. Por otro lado, la capacidad de las HDL de ratones hiperhomocisteinémicos de prevenir la modificación oxidativa de las lipoproteínas de baja densidad (LDL) disminuyó, observándose también una reducción en la actividad plasmática de paraoxonasa-1 (PON1) y en la concentración plasmática de apoA- I y con una disminución relativa en la cantidad de apoA- IV (∼ 1,5 veces) en las HDL de ratones hiperhomocisteinémicos comparados con las de los controles. Conclusión La disminución en la protección contra la modificación oxidativa de las LDL por parte de las HDL de ratones hiperhomocisteinémicos se asoció con una disminución de apoA- I , PON1 y apoA- IV

AIM: The aim of this study was to evaluate the proteic changes in high-density lipoproteins(HDL) induced by methionine-induced hyperhomocysteinemia in mice and its relationship with two of their main antiatherogenic properties. METHODS AND RESULTS: The oral administration of methionine resulted in an elevation (∼ 8 times)in the plasma concentration of homocysteine. Hyperhomocysteinemia was inversely correlated with the plasma concentration of HDL cholesterol and its main protein component of HDL, apolipoprotein (apo) A-I, respectively. The cholesterol efflux in vivo from macrophages to HDL was decreased in hyperhomocysteinemic mice compared with the control mice. However, the reverse cholesterol transport from macrophages to feces remained unchanged. On the other hand, the ability of HDL from hyperhomocysteinemic mice to prevent the oxidative modification of low-density lipoproteins (LDL) was found decreased and associated with a concomitant reduction in the plasma activity of paraoxonase-1 (PON1) and the plasma concentration of apoA-I, and with a relative reduction in the apoA-IV content (∼1.5times) in the hyperhomocysteinemic HDL, respectively. Conclusion: The decrease in the ability of HDL from hyperhomocysteinemic mice to prevent LDL from oxidation was associated with a decrease in the apoA-I, PON1 and apoA-IV

[Alterations in the protein content and dysfunction of high-density lipoproteins from hyperhomocysteinemic mice]. / Alteraciones en el contenido proteico y disfunción de lipoproteínas de alta densidad en ratones hiperhomocisteinémicos.

AIM: The aim of this study was to evaluate the proteic changes in high-density lipoproteins (HDL) induced by methionine-induced hyperhomocysteinemia in mice and its relationship with two of their main antiatherogenic properties. METHODS AND RESULTS: The oral administration of methionine resulted in an elevation (~8 times) in the plasma concentration of homocysteine. Hyperhomocysteinemia was inversely correlated with the plasma concentration of HDL cholesterol and its main protein component of HDL, apolipoprotein (apo) A-I, respectively. The cholesterol efflux in vivo from macrophages to HDL was decreased in hyperhomocysteinemic mice compared with the control mice. However, the reverse cholesterol transport from macrophages to feces remained unchanged. On the other hand, the ability of HDL from hyperhomocysteinemic mice to prevent the oxidative modification of low-density lipoproteins (LDL) was found decreased and associated with a concomitant reduction in the plasma activity of paraoxonase-1 (PON1) and the plasma concentration of apoA-I, and with a relative reduction in the apoA-IV content (~1.5 times) in the hyperhomocysteinemic HDL, respectively. CONCLUSION: The decrease in the ability of HDL from hyperhomocysteinemic mice to prevent LDL from oxidation was associated with a decrease in the apoA-I, PON1 and apoA-IV.