Hua-Chen Chan1, Hsiu-Chuan Chan2, Chan-Jung Liang3, Hsiang-Chun Lee4, Hung Su5, An-Sheng Lee6, Jentaie Shiea5, Wen-Chan Tsai7, Tsan-Teng Ou7, Cheng-Chin Wu7, Chih-Sheng Chu4, Richard A Dixon8, Liang-Yin Ke4, Jeng-Hsien Yen9, Chu-Huang Chen10. 1. Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan, and Texas Heart Institute, Houston. 2. Kaohsiung Medical University, Kaohsiung, Taiwan, and Texas Heart Institute, Houston. 3. Kaohsiung Medical University, Kaohsiung, Taiwan. 4. Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan. 5. National Sun Yat-sen University, Kaohsiung, Taiwan. 6. Mackay Medical College, New Taipei, Taiwan. 7. Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 8. Texas Heart Institute, Houston. 9. Kaohsiung Medical University Hospital, Kaohsiung Medical University, and National Sun Yat-sen University, Kaohsiung, Taiwan, and National Chiao Tung University, Hsinchu, Taiwan. 10. Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan, and Texas Heart Institute, Houston, and New York Heart Research Foundation, Mineola.
Abstract
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.
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 SLEpatients. METHODS: Plasma LDL from 45 SLEpatients (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 SLEpatients 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 SLEpatients. 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 SLEpatients, leading to premature atherosclerosis.
Authors: Kirsty E Waddington; George A Robinson; Leda Coelewij; Elvira Chocano; Thomas McDonnell; Filipa Farinha; Junjie Peng; Pierre Dönnes; Edward Smith; Sara Croca; Jyoti Bakshi; Maura Griffin; Andrew Nicolaides; Anisur Rahman; Elizabeth C Jury; Ines Pineda-Torra Journal: Arterioscler Thromb Vasc Biol Date: 2021-02-04 Impact factor: 10.514
Authors: Der-Yuan Chen; Tatsuya Sawamura; Richard A F Dixon; José Luis Sánchez-Quesada; Chu-Huang Chen Journal: J Clin Med Date: 2021-05-06 Impact factor: 4.241