دورية أكاديمية
LOX-1: A potential driver of cardiovascular risk in SLE patients.
| العنوان: | LOX-1: A potential driver of cardiovascular risk in SLE patients. |
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| المؤلفون: | Sagar D; Respiratory, Inflammation and Autoimmune, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States of America., Gaddipati R; Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States of America., Ongstad EL; Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States of America., Bhagroo N; Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States of America., An LL; Respiratory, Inflammation and Autoimmune, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States of America., Wang J; Respiratory, Inflammation and Autoimmune, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States of America., Belkhodja M; Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States of America., Rahman S; Respiratory, Inflammation and Autoimmune, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States of America., Manna Z; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Health, Bethesda, Maryland, United States of America., Davis MA; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Health, Bethesda, Maryland, United States of America., Hasni S; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Health, Bethesda, Maryland, United States of America., Siegel R; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Health, Bethesda, Maryland, United States of America., Sanjuan M; Respiratory, Inflammation and Autoimmune, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States of America., Grimsby J; Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States of America., Kolbeck R; Respiratory, Inflammation and Autoimmune, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States of America., Karathanasis S; Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States of America., Sims GP; Respiratory, Inflammation and Autoimmune, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States of America., Gupta R; Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States of America. |
| المصدر: | PloS one [PLoS One] 2020 Mar 17; Vol. 15 (3), pp. e0229184. Date of Electronic Publication: 2020 Mar 17 (Print Publication: 2020). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science |
| مواضيع طبية MeSH: | Cardiovascular Diseases/*etiology , Lupus Erythematosus, Systemic/*blood , Lupus Erythematosus, Systemic/*complications , Scavenger Receptors, Class E/*physiology, Adult ; Atherosclerosis/blood ; Atherosclerosis/complications ; Cardiovascular Diseases/blood ; Case-Control Studies ; Disease Progression ; Female ; Humans ; Inflammation/blood ; Inflammation/complications ; Lupus Erythematosus, Systemic/pathology ; Male ; Middle Aged ; Risk Factors ; Scavenger Receptors, Class E/blood ; Young Adult |
| مستخلص: | 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. Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: DS, RG, ELO, NB, L-LA, JW, MB, SR, MS, JG, RK, SK, GPS and RG are all current employees of MedImmune/AstraZeneca with stock options in AstraZeneca, or former employees of MedImmune/AstraZeneca. MedImmune/AstraZeneca has patents for the use of anti-LOX-1 Ab in the treatment of cardiovascular disease. This does not alter our adherence to PLOS ONE policies on sharing data and materials. ZM, MAD, SH, and RS have no competing interests. |
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| المشرفين على المادة: | 0 (OLR1 protein, human) 0 (Scavenger Receptors, Class E) |
| تواريخ الأحداث: | Date Created: 20200318 Date Completed: 20200617 Latest Revision: 20200617 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC7077835 |
| DOI: | 10.1371/journal.pone.0229184 |
| PMID: | 32182251 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1932-6203 |
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| DOI: | 10.1371/journal.pone.0229184 |