LOX-1: A potential driver of cardiovascular risk in SLE patients.
Traditional cardiovascular disease (CVD) risk factors, such as hypertension, dyslipidemia and diabetes do not explain the increased CVD burden in systemic lupus erythematosus (SLE). The oxidized-LDL receptor, LOX-1, is an inflammation-induced receptor implicated in atherosclerotic plaque formation i...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0229184 |
| _version_ | 1818581452071108608 |
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| author | Divya Sagar Ranjitha Gaddipati Emily L Ongstad Nicholas Bhagroo Ling-Ling An Jingya Wang Mehdi Belkhodja Saifur Rahman Zerai Manna Michael A Davis Sarfaraz Hasni Richard Siegel Miguel Sanjuan Joseph Grimsby Roland Kolbeck Sotirios Karathanasis Gary P Sims Ruchi Gupta |
| author_facet | Divya Sagar Ranjitha Gaddipati Emily L Ongstad Nicholas Bhagroo Ling-Ling An Jingya Wang Mehdi Belkhodja Saifur Rahman Zerai Manna Michael A Davis Sarfaraz Hasni Richard Siegel Miguel Sanjuan Joseph Grimsby Roland Kolbeck Sotirios Karathanasis Gary P Sims Ruchi Gupta |
| author_sort | Divya Sagar |
| collection | DOAJ |
| description | Traditional cardiovascular disease (CVD) risk factors, such as hypertension, dyslipidemia and diabetes do not explain the increased CVD burden in systemic lupus erythematosus (SLE). The oxidized-LDL receptor, LOX-1, is an inflammation-induced receptor implicated in atherosclerotic plaque formation in acute coronary syndrome, and here we evaluated its role in SLE-associated CVD. SLE patients have increased sLOX-1 levels which were associated with elevated proinflammatory HDL, oxLDL and hsCRP. Interestingly, increased sLOX-1 levels were associated with patients with early disease onset, low disease activity, increased IL-8, and normal complement and hematological measures. LOX-1 was increased on patient-derived monocytes and low-density granulocytes, and activation with oxLDL and immune-complexes increased membrane LOX-1, TACE activity, sLOX-1 release, proinflammatory cytokine production by monocytes, and triggered the formation of neutrophil extracellular traps which can promote vascular injury. In conclusion, perturbations in the lipid content in SLE patients' blood activate LOX-1 and promote inflammatory responses. Increased sLOX-1 levels may be an indicator of high CVD risk, and blockade of LOX-1 may provide a therapeutic opportunity for ameliorating atherosclerosis in SLE patients. |
| first_indexed | 2024-12-16T07:33:43Z |
| format | Article |
| id | doaj.art-9492d65c815e46fd9c7305beb5282253 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T07:33:43Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9492d65c815e46fd9c7305beb52822532022-12-21T22:39:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01153e022918410.1371/journal.pone.0229184LOX-1: A potential driver of cardiovascular risk in SLE patients.Divya SagarRanjitha GaddipatiEmily L OngstadNicholas BhagrooLing-Ling AnJingya WangMehdi BelkhodjaSaifur RahmanZerai MannaMichael A DavisSarfaraz HasniRichard SiegelMiguel SanjuanJoseph GrimsbyRoland KolbeckSotirios KarathanasisGary P SimsRuchi GuptaTraditional cardiovascular disease (CVD) risk factors, such as hypertension, dyslipidemia and diabetes do not explain the increased CVD burden in systemic lupus erythematosus (SLE). The oxidized-LDL receptor, LOX-1, is an inflammation-induced receptor implicated in atherosclerotic plaque formation in acute coronary syndrome, and here we evaluated its role in SLE-associated CVD. SLE patients have increased sLOX-1 levels which were associated with elevated proinflammatory HDL, oxLDL and hsCRP. Interestingly, increased sLOX-1 levels were associated with patients with early disease onset, low disease activity, increased IL-8, and normal complement and hematological measures. LOX-1 was increased on patient-derived monocytes and low-density granulocytes, and activation with oxLDL and immune-complexes increased membrane LOX-1, TACE activity, sLOX-1 release, proinflammatory cytokine production by monocytes, and triggered the formation of neutrophil extracellular traps which can promote vascular injury. In conclusion, perturbations in the lipid content in SLE patients' blood activate LOX-1 and promote inflammatory responses. Increased sLOX-1 levels may be an indicator of high CVD risk, and blockade of LOX-1 may provide a therapeutic opportunity for ameliorating atherosclerosis in SLE patients.https://doi.org/10.1371/journal.pone.0229184 |
| spellingShingle | Divya Sagar Ranjitha Gaddipati Emily L Ongstad Nicholas Bhagroo Ling-Ling An Jingya Wang Mehdi Belkhodja Saifur Rahman Zerai Manna Michael A Davis Sarfaraz Hasni Richard Siegel Miguel Sanjuan Joseph Grimsby Roland Kolbeck Sotirios Karathanasis Gary P Sims Ruchi Gupta LOX-1: A potential driver of cardiovascular risk in SLE patients. PLoS ONE |
| title | LOX-1: A potential driver of cardiovascular risk in SLE patients. |
| title_full | LOX-1: A potential driver of cardiovascular risk in SLE patients. |
| title_fullStr | LOX-1: A potential driver of cardiovascular risk in SLE patients. |
| title_full_unstemmed | LOX-1: A potential driver of cardiovascular risk in SLE patients. |
| title_short | LOX-1: A potential driver of cardiovascular risk in SLE patients. |
| title_sort | lox 1 a potential driver of cardiovascular risk in sle patients |
| url | https://doi.org/10.1371/journal.pone.0229184 |
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