期刊
ATHEROSCLEROSIS
卷 266, 期 -, 页码 48-57出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2017.09.021
关键词
Familial hypercholesterolemia; LDL cholesterol; Lipids; Children; Metabolomics; Metabolic profiling
资金
- University of Oslo, Oslo, Norway
- National Advisory Unit on FH, Oslo University Hospital, Oslo, Norway
- Throne-Holst Foundation for Nutrition Research, Oslo, Norway
- Vita Hjertego' Grant, Norway
- South-Eastern Regional Health Authority, Oslo, Norway
Background and aims: Individuals with familial hypercholesterolemia (FH) have elevated low-density lipoprotein cholesterol (LDL-C), accelerated atherosclerosis, and premature cardiovascular disease. Whereas children with lifestyle-induced dyslipidemias often present with complex lipid abnormalities, children with FH have isolated hypercholesterolemia. However, to the best of our knowledge, a comprehensive profiling of FH children is lacking. Therefore, we aimed to characterize the lipid-related and metabolic alterations associated with elevated LDL-C in children with FH and healthy children. Methods: We measured plasma metabolites in children with FH (n = 47) and in healthy children (n = 57) using a high-throughput nuclear magnetic resonance (NMR) spectroscopy platform, and compared the differences between FH and healthy children. Results: Both statin treated (n = 17) and non-statin treated FH children (n = 30) had higher levels of atherogenic ApoB-containing lipoproteins and lipids, and lipid fractions in lipoprotein subclasses, compared to healthy children (n = 57). FH children displayed alterations in HDL particle concentration and lipid content, compared with healthy children. Interestingly, the small HDL particles were characterized by higher content of cholesteryl esters, and lower levels of free cholesterol and phospholipids. Furthermore, plasma fatty acids were higher in non-statin treated FH children, particularly linoleic acid. Finally, acetoacetate and acetate were lower in FH children compared with healthy children. Conclusions: Hypercholesterolemia in children associates with diverse metabolic repercussions and is more complex than previously believed. In particular, we found that hypercholesterolemia in FH children was paralleled not only by increased atherogenic ApoB-containing lipoproteins and lipid fractions, but also alterations in HDL subfractions that suggest impaired reverse cholesterol transport. (C) 2017 Elsevier B.V. All rights reserved.
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