کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5843430 | 1560829 | 2016 | 39 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
ApoA-IMilano phospholipid complex (ETC-216) infusion in human volunteers. Insights into the phenotypic characteristics of ApoA-IMilano carriers
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Epidemiological studies support an inverse correlation between HDL-C and cardiovascular disease. However, low HDL-C levels do not always segregate with premature disease. These include, LCAT deficiency and the apolipoproteinA-IMilano (AIM) variant. AIM has a cysteine for arginine at position 173 in the otherwise cysteine free protein permitting AIM homodimerization and apoA-II heterodimerization. We relate the biochemical characteristics of low HDL-C phenotype AIM carriers to lipoprotein changes in humans administered recombinant dimeric AIM/palmitoyl-oleoyl phosphatidyl choline (ETC-216). Pharmacokinetic analysis of infused ETC-216 suggest a slow distribution of AIM into peripheral tissue and an extremely long terminal half-life in plasma. Following ETC-216 administration to normal human volunteers, an initial dose-dependent HDL-C elevation was observed. Thereafter, subjects transiently acquired a lipoprotein profile similar to that of AIM carriers, including reduced HDL-C and mild hypertriglyceridemia. The time-dependent changes in plasma lipids/lipoproteins may support an increased tissue cholesterol removing capacity of ETC-216. These findings provide mechanistic insight into the rapid removal of atheromatous plaques observed in humans, possibly linked to enhanced cholesterol removal capacity of ETC-216.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacological Research - Volume 111, September 2016, Pages 86-99
Journal: Pharmacological Research - Volume 111, September 2016, Pages 86-99
نویسندگان
Charles L. Bisgaier, Rose Ackermann, Thomas Rea, Wendi V. Rodrigueza, Daniel Hartman,