Acute impact of apheresis on oxidized phospholipids in patients with familial hypercholesterolemia1
We measured oxidized phospholipids (OxPL), lipoprotein (a) [Lp(a)], and lipoprotein-associated phospholipase A2 (Lp-PLA2) pre- and postapheresis in 18 patients with familial hypercholesterolemia (FH) and with low(∼10 mg/dl; range 10–11 mg/dl), intermediate (∼50 mg/dl; range 30–61 mg/dl), or high (&g...
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| Format: | Article |
| Language: | English |
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Elsevier
2012-08-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520418711 |
| _version_ | 1818386401936277504 |
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| author | Kiyohito Arai Alexina Orsoni Ziad Mallat Alain Tedgui Joseph L. Witztum Eric Bruckert Alexandros D. Tselepis M. John Chapman Sotirios Tsimikas |
| author_facet | Kiyohito Arai Alexina Orsoni Ziad Mallat Alain Tedgui Joseph L. Witztum Eric Bruckert Alexandros D. Tselepis M. John Chapman Sotirios Tsimikas |
| author_sort | Kiyohito Arai |
| collection | DOAJ |
| description | We measured oxidized phospholipids (OxPL), lipoprotein (a) [Lp(a)], and lipoprotein-associated phospholipase A2 (Lp-PLA2) pre- and postapheresis in 18 patients with familial hypercholesterolemia (FH) and with low(∼10 mg/dl; range 10–11 mg/dl), intermediate (∼50 mg/dl; range 30–61 mg/dl), or high (>100 mg/dl; range 78–128 mg/dl) Lp(a) levels. By using enzymatic and immunoassays, the content of OxPL and Lp-PLA2 mass and activity were quantitated in lipoprotein density fractions plated in microtiter wells, as well as directly on apoB-100, Lp(a), and apoA-I immunocaptured within each fraction (i.e., OxPL/apoB and Lp-PLA2/apoB). In whole fractions, OxPL was primarily detected in the Lp(a)-containing fractions, whereas Lp-PLA2 was primarily detected in the small, dense LDL and light Lp(a) range. In lipoprotein capture assays, OxPL/apoB and OxPL/apo(a) increased proportionally with increasing Lp(a) levels. Lp-PLA2/apoB and Lp-PLA2/apoA-I levels were highest in the low Lp(a) group but decreased proportionally with increasing Lp(a) levels. Lp-PLA2/apo(a) was lowest in patients with low Lp(a) levels and increased proportionally with increasing Lp(a) levels. Apheresis significantly reduced levels of OxPL and Lp-PLA2 on apoB and Lp(a) (50–75%), particularly in patients with intermediate and high Lp(a) levels. In contrast, apheresis increased Lp-PLA2-specific activity (activity/mass ratio) in buoyant LDL fractions. The impact of apheresis on Lp(a), OxPL, and Lp-PLA2 provides insights into its therapeutic benefits beyond lowering apoB-containing lipoproteins. |
| first_indexed | 2024-12-14T03:53:28Z |
| format | Article |
| id | doaj.art-ff6c11af60734bee902f9cce45797669 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T03:53:28Z |
| publishDate | 2012-08-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj.art-ff6c11af60734bee902f9cce457976692022-12-21T23:18:09ZengElsevierJournal of Lipid Research0022-22752012-08-0153816701678Acute impact of apheresis on oxidized phospholipids in patients with familial hypercholesterolemia1Kiyohito Arai0Alexina Orsoni1Ziad Mallat2Alain Tedgui3Joseph L. Witztum4Eric Bruckert5Alexandros D. Tselepis6M. John Chapman7Sotirios Tsimikas8Tokyo Women's University, Tokyo, Japan; University of California San Diego, La Jolla, CADyslipidemia and Atherosclerosis Research Unit, INSERM UMR-S939, University of Pierre et Marie Curie, Paris, FranceDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom; Paris Cardiovascular Research Center, Inserm U 970, Paris-Descartes University, Paris, France; andParis Cardiovascular Research Center, Inserm U 970, Paris-Descartes University, Paris, France; andTokyo Women's University, Tokyo, JapanDyslipidemia and Atherosclerosis Research Unit, INSERM UMR-S939, University of Pierre et Marie Curie, Paris, FranceUniversity of Ioannina, Ioannina, GreeceDyslipidemia and Atherosclerosis Research Unit, INSERM UMR-S939, University of Pierre et Marie Curie, Paris, FranceTo whom correspondence should be addressed. e-mail: stsimikas@ucsd.edu.; Tokyo Women's University, Tokyo, Japan; To whom correspondence should be addressed. e-mail: stsimikas@ucsd.edu.We measured oxidized phospholipids (OxPL), lipoprotein (a) [Lp(a)], and lipoprotein-associated phospholipase A2 (Lp-PLA2) pre- and postapheresis in 18 patients with familial hypercholesterolemia (FH) and with low(∼10 mg/dl; range 10–11 mg/dl), intermediate (∼50 mg/dl; range 30–61 mg/dl), or high (>100 mg/dl; range 78–128 mg/dl) Lp(a) levels. By using enzymatic and immunoassays, the content of OxPL and Lp-PLA2 mass and activity were quantitated in lipoprotein density fractions plated in microtiter wells, as well as directly on apoB-100, Lp(a), and apoA-I immunocaptured within each fraction (i.e., OxPL/apoB and Lp-PLA2/apoB). In whole fractions, OxPL was primarily detected in the Lp(a)-containing fractions, whereas Lp-PLA2 was primarily detected in the small, dense LDL and light Lp(a) range. In lipoprotein capture assays, OxPL/apoB and OxPL/apo(a) increased proportionally with increasing Lp(a) levels. Lp-PLA2/apoB and Lp-PLA2/apoA-I levels were highest in the low Lp(a) group but decreased proportionally with increasing Lp(a) levels. Lp-PLA2/apo(a) was lowest in patients with low Lp(a) levels and increased proportionally with increasing Lp(a) levels. Apheresis significantly reduced levels of OxPL and Lp-PLA2 on apoB and Lp(a) (50–75%), particularly in patients with intermediate and high Lp(a) levels. In contrast, apheresis increased Lp-PLA2-specific activity (activity/mass ratio) in buoyant LDL fractions. The impact of apheresis on Lp(a), OxPL, and Lp-PLA2 provides insights into its therapeutic benefits beyond lowering apoB-containing lipoproteins.http://www.sciencedirect.com/science/article/pii/S0022227520418711atherogenesisinflammationmyocardial infarction |
| spellingShingle | Kiyohito Arai Alexina Orsoni Ziad Mallat Alain Tedgui Joseph L. Witztum Eric Bruckert Alexandros D. Tselepis M. John Chapman Sotirios Tsimikas Acute impact of apheresis on oxidized phospholipids in patients with familial hypercholesterolemia1 Journal of Lipid Research atherogenesis inflammation myocardial infarction |
| title | Acute impact of apheresis on oxidized phospholipids in patients with familial hypercholesterolemia1 |
| title_full | Acute impact of apheresis on oxidized phospholipids in patients with familial hypercholesterolemia1 |
| title_fullStr | Acute impact of apheresis on oxidized phospholipids in patients with familial hypercholesterolemia1 |
| title_full_unstemmed | Acute impact of apheresis on oxidized phospholipids in patients with familial hypercholesterolemia1 |
| title_short | Acute impact of apheresis on oxidized phospholipids in patients with familial hypercholesterolemia1 |
| title_sort | acute impact of apheresis on oxidized phospholipids in patients with familial hypercholesterolemia1 |
| topic | atherogenesis inflammation myocardial infarction |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520418711 |
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