Effect of gestational hypercholesterolemia and maternal immunization on offspring plasma eicosanoids

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• 作者：Oswald Quehenberger ; PhD^a ; Tomoya Yamashita ; MD ; PhD^a ; ^c ; Aaron M. Armando ; BS^b ; Edward A. Dennis ; PhD^b ; Wulf Palinski ; MD^a
• 关键词：cardiovascular disease ; developmental programming ; eicosanoids ; immunization ; inflammation ; rabbits
• 刊名：American Journal of Obstetrics and Gynecology
• 出版年：2011
• 出版时间：August, 2011
• 年：2011
• 卷：205
• 期：2
• 页码：156.e15-156.e25
• 全文大小：3412 K

文摘

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Objective

Maternal immunization with oxidized low-density lipoprotein prior to pregnancy prevents pathogenic in utero programming by gestational hypercholesterolemia, but it is unknown whether gestational hypercholesterolemia and maternal immunization affect similar pathways.

Study Design

A lipidomic approach was used for unbiased plasma eicosanoid profiling in adult offspring of immunized and nonimmunized normocholesterolemic or hypercholesterolemic rabbit mothers.

Results

Gestational hypercholesterolemia was associated with increased levels of some eicosanoids formed by the cyclooxygenase and 12-lipoxygenase pathways only (including thromboxane B₂, prostaglandin [PG] F_2¦Á, PGE₂, and PGD₂). Immunization of hypercholesterolemic or normocholesterolemic mothers reduced 9 of 14 eicosanoids of the cyclooxygenase pathway, 21 of 23 eicosanoids of the 5- and 12-lipoxygenase pathways (eg, 5-hydroxyeicosatetraenoic acid, hepoxilin B₃, 12-hydroxyeicosatetraenoic acid), 8 of 19 eicosanoids of the cytochrome P-450 pathway, and all metabolites of the nonenzymatic pathway.

Conclusion

Maternal immunization not only counteracts in utero programming by gestational hypercholesterolemia but reduces a broad range of eicosanoid modulators of immunity and inflammation in offspring.