Role of Low-Density Lipoprotein in Early Vascular Aging Associated With Systemic Lupus Erythematosus
© 2020, American College of Rheumatology..
OBJECTIVE: Patients with systemic lupus erythematosus (SLE) often have atherosclerotic complications at a young age but normal low-density lipoprotein (LDL) levels. This study was undertaken to investigate the role of LDL composition in promoting early vascular aging in SLE patients.
METHODS: Plasma LDL from 45 SLE patients (SLE-LDL) and from 37 normal healthy controls (N-LDL) was chromatographically divided into 5 subfractions (L1-L5), and the subfraction composition was analyzed. Correlations between subfraction levels and signs of early vascular aging were assessed. Mechanisms of lipid-mediated endothelial dysfunction were explored using in vitro assays and experiments in apoE-/- mice.
RESULTS: The L5 percentage was increased 3.4 times in the plasma of SLE patients compared with normal controls. This increased percentage of SLE-L5 was positively correlated with the mean blood pressure (r = 0.27, P = 0.04), carotid intima-media thickness (IMT) (right carotid IMT, r = 0.4, P = 0.004; left carotid IMT, r = 0.36, P = 0.01), pulse wave velocity (r = 0.29, P = 0.04), and blood levels of CD16+ monocytes (r = 0.35, P = 0.004) and CX3CL1 cytokines (r = 0.43, P < 0.001) in SLE patients. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis revealed that plasma levels of lysophosphatidylcholine (LPC) and platelet-activating factor (PAF) were increased in SLE-LDL and in the SLE-L5 plasma subfraction. Injecting SLE-LDL, SLE-L5, or LPC into young, male apoE-/- mice caused increases in plasma CX3CL1 levels, aortic fatty-streak areas, aortic vascular aging, and macrophage infiltration into the aortic wall, whereas injection of N-LDL or SLE-L1 had negligible effects (n = 3-8 mice per group). In vitro, SLE-L5 lipid extracts induced increases in CX3CR1 and CD16 expression in human monocytes; synthetic PAF and LPC had similar effects. Furthermore, lipid extracts of SLE-LDL and SLE-L5 induced the expression of CX3CL1 and enhanced monocyte-endothelial cell adhesion in assays with bovine aortic endothelial cells.
CONCLUSION: An increase in plasma L5 levels, not total LDL concentration, may promote early vascular aging in SLE patients, leading to premature atherosclerosis.
| Errataetall: |
CommentIn: Nat Rev Rheumatol. 2020 Apr;16(4):187. - PMID 32094755 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:72 |
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| Enthalten in: |
Arthritis & rheumatology (Hoboken, N.J.) - 72(2020), 6 vom: 01. Juni, Seite 972-984 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chan, Hua-Chen [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 22.07.2020 Date Revised 22.07.2020 published: Print-Electronic CommentIn: Nat Rev Rheumatol. 2020 Apr;16(4):187. - PMID 32094755 Citation Status MEDLINE |
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| doi: |
10.1002/art.41213 |
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| Förderinstitution / Projekttitel: |
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NLM305902687 |
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| 500 | |a Date Completed 22.07.2020 | ||
| 500 | |a Date Revised 22.07.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Nat Rev Rheumatol. 2020 Apr;16(4):187. - PMID 32094755 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020, American College of Rheumatology. | ||
| 520 | |a OBJECTIVE: Patients with systemic lupus erythematosus (SLE) often have atherosclerotic complications at a young age but normal low-density lipoprotein (LDL) levels. This study was undertaken to investigate the role of LDL composition in promoting early vascular aging in SLE patients | ||
| 520 | |a METHODS: Plasma LDL from 45 SLE patients (SLE-LDL) and from 37 normal healthy controls (N-LDL) was chromatographically divided into 5 subfractions (L1-L5), and the subfraction composition was analyzed. Correlations between subfraction levels and signs of early vascular aging were assessed. Mechanisms of lipid-mediated endothelial dysfunction were explored using in vitro assays and experiments in apoE-/- mice | ||
| 520 | |a RESULTS: The L5 percentage was increased 3.4 times in the plasma of SLE patients compared with normal controls. This increased percentage of SLE-L5 was positively correlated with the mean blood pressure (r = 0.27, P = 0.04), carotid intima-media thickness (IMT) (right carotid IMT, r = 0.4, P = 0.004; left carotid IMT, r = 0.36, P = 0.01), pulse wave velocity (r = 0.29, P = 0.04), and blood levels of CD16+ monocytes (r = 0.35, P = 0.004) and CX3CL1 cytokines (r = 0.43, P < 0.001) in SLE patients. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis revealed that plasma levels of lysophosphatidylcholine (LPC) and platelet-activating factor (PAF) were increased in SLE-LDL and in the SLE-L5 plasma subfraction. Injecting SLE-LDL, SLE-L5, or LPC into young, male apoE-/- mice caused increases in plasma CX3CL1 levels, aortic fatty-streak areas, aortic vascular aging, and macrophage infiltration into the aortic wall, whereas injection of N-LDL or SLE-L1 had negligible effects (n = 3-8 mice per group). In vitro, SLE-L5 lipid extracts induced increases in CX3CR1 and CD16 expression in human monocytes; synthetic PAF and LPC had similar effects. Furthermore, lipid extracts of SLE-LDL and SLE-L5 induced the expression of CX3CL1 and enhanced monocyte-endothelial cell adhesion in assays with bovine aortic endothelial cells | ||
| 520 | |a CONCLUSION: An increase in plasma L5 levels, not total LDL concentration, may promote early vascular aging in SLE patients, leading to premature atherosclerosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Lipoproteins, LDL |2 NLM | |
| 700 | 1 | |a Chan, Hsiu-Chuan |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Chan-Jung |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Hsiang-Chun |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Hung |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, An-Sheng |e verfasserin |4 aut | |
| 700 | 1 | |a Shiea, Jentaie |e verfasserin |4 aut | |
| 700 | 1 | |a Tsai, Wen-Chan |e verfasserin |4 aut | |
| 700 | 1 | |a Ou, Tsan-Teng |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Cheng-Chin |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Chih-Sheng |e verfasserin |4 aut | |
| 700 | 1 | |a Dixon, Richard A |e verfasserin |4 aut | |
| 700 | 1 | |a Ke, Liang-Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Yen, Jeng-Hsien |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chu-Huang |e verfasserin |4 aut | |
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