Intravenous Injection of Apolipoprotein A-V Reconstituted High-Density Lipoprotein Decreases Hypertriglyceridemia in apoav −/− Mice and Requires Glycosylphosphatidylinositol-Anchored High-Density Lipoprotein–Binding Protein 1
| العنوان: | Intravenous Injection of Apolipoprotein A-V Reconstituted High-Density Lipoprotein Decreases Hypertriglyceridemia in apoav −/− Mice and Requires Glycosylphosphatidylinositol-Anchored High-Density Lipoprotein–Binding Protein 1 |
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| المؤلفون: | Trudy M. Forte, Robert O. Ryan, Stephen G. Young, Michael M. Weinstein, Xiao Shu, Jennifer A. Beckstead, Braydon L. Burgess, Lisa Nelbach |
| المصدر: | Arteriosclerosis, Thrombosis, and Vascular Biology. 30:2504-2509 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | medicine.medical_specialty, Triglyceride, Binding protein, Hypertriglyceridemia, nutritional and metabolic diseases, Metabolism, Apolipoproteins A, Biology, medicine.disease, chemistry.chemical_compound, Endocrinology, High-density lipoprotein, chemistry, Internal medicine, polycyclic compounds, medicine, lipids (amino acids, peptides, and proteins), Binding site, Cardiology and Cardiovascular Medicine, Lipoprotein |
| الوصف: | Objective— Apolipoprotein A-V (apoA-V), a minor protein associated with lipoproteins, has a major effect on triacylglycerol (TG) metabolism. We investigated whether apoA-V complexed with phospholipid in the form of a reconstituted high-density lipoprotein (rHDL) has potential utility as a therapeutic agent for treatment of hypertriglyceridemia (HTG) when delivered intravenously. Methods and Results— Intravenous injection studies were performed in genetically engineered mouse models of severe HTG, including apoav −/− and gpihbp1 −/− mice. Administration of apoA-V rHDL to hypertriglyceridemic apoav −/− mice resulted in a 60% reduction in plasma TG concentration after 4 hours. This decline can be attributed to enhanced catabolism/clearance of very-low-density lipoprotein (VLDL), where VLDL TG and cholesterol were reduced ≈60%. ApoA-V that associated with VLDL after injection was also rapidly cleared. Site-specific mutations in the heparin-binding region of apoA-V (amino acids 186 to 227) attenuated apoA-V rHDL TG-lowering activity by 50%, suggesting that this sequence element is required for optimal TG-lowering activity in vivo. Unlike apoav −/− mice, injection of apoA-V rHDL into gpihbp1 −/− mice had no effect on plasma TG levels, and apoA-V remained associated with plasma VLDL. Conclusion— Intravenously injected apoA-V rHDL significantly lowers plasma TG in an apoA-V deficient mouse model. Its intravenous administration may have therapeutic benefit in human subjects with severe HTG, especially in cases involving apoA-V variants associated with HTG. |
| تدمد: | 1524-4636 1079-5642 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::6735512a63c50336201a7d74d0133c55 https://doi.org/10.1161/atvbaha.110.210815 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........6735512a63c50336201a7d74d0133c55 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244636 10795642 |
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