Elevated Lipoprotein(a) Levels Lower ABCA1 Cholesterol Efflux Capacity
| العنوان: | Elevated Lipoprotein(a) Levels Lower ABCA1 Cholesterol Efflux Capacity |
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| المؤلفون: | Sara Rosario, Joshua Miles, Jessica Minnier, Rayna Gasik, Nathalie Pamir, Deanna L. Plubell, Hagai Tavori, Sergio Fazio, Elisabeth Yerkes, Alexandra M Fenton, Paige Bergstrom |
| المصدر: | The Journal of Clinical Endocrinology & Metabolism. 104:4793-4803 |
| بيانات النشر: | The Endocrine Society, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Context (language use), 030204 cardiovascular system & hematology, Biochemistry, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Cricetinae, Internal medicine, medicine, Baby hamster kidney cell, Animals, Humans, In patient, Clinical Research Articles, Cells, Cultured, biology, Chemistry, Cholesterol, Macrophages, Biochemistry (medical), Biological Transport, Lipoprotein(a), Fibroblasts, Middle Aged, 030104 developmental biology, ABCA1, biology.protein, lipids (amino acids, peptides, and proteins), Female, Efflux, ATP Binding Cassette Transporter 1, Lipoprotein |
| الوصف: | ContextElevated serum lipoprotein(a) [Lp(a)] levels are associated with increased cardiovascular disease risk. ABCA1-mediated cholesterol efflux from macrophages may be an antiatherogenic process. Plasminogen (PLG) is a driver of ABCA1-mediated cholesterol efflux, and its action is inhibited by purified human Lp(a).ObjectiveTo determine the effects of Lp(a) in human serum on ABCA1 cholesterol efflux.MethodsCholesterol efflux capacity (CEC) was measured with two different cell-culture models using serum from 76 patients with either low (50 mg/dL) Lp(a) levels.ResultsUsing cAMP-stimulated J774 macrophages or baby hamster kidney fibroblasts overexpressing human ABCA1, we show that CEC was lower in patients with high Lp(a) levels compared with patients with low levels (−30.6%, P = 0.002 vs −24.1%, P < 0.001, respectively). Total-serum CEC negatively correlated with Lp(a) levels (r = −0.433, P = 0.0007 vs r = −0.505, P = 0.0011, respectively). These negative associations persisted after adjusting for serum cholesterol, age, sex, and statin use in a multiple linear regression model (adjusted R2 = 0.413 or 0.405, respectively) and were strengthened when further adjusting for the interaction between Lp(a) and PLG levels (adjusted R2 = 0.465 and 0.409, respectively). Total-serum and isolated Lp(a) from patients with high Lp(a) inhibited PLG-mediated ABCA1 cholesterol efflux.ConclusionTotal-serum CEC is reduced in patients with high Lp(a) levels. This is in part due to the inhibition of PLG-mediated ABCA1 cholesterol efflux by Lp(a). Our findings suggest an atherogenic role for Lp(a) through its ability to inhibit CEC. |
| تدمد: | 1945-7197 0021-972X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0afface0c8c058b8bd88bff8780aa9baTest https://doi.org/10.1210/jc.2018-02708Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0afface0c8c058b8bd88bff8780aa9ba |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19457197 0021972X |
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