دورية أكاديمية
The Fungal Iron Chelator Desferricoprogen Inhibits Atherosclerotic Plaque Formation
| العنوان: | The Fungal Iron Chelator Desferricoprogen Inhibits Atherosclerotic Plaque Formation |
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| المؤلفون: | László Potor, Katalin Éva Sikura, Hajnalka Hegedűs, Dávid Pethő, Zsuzsa Szabó, Zsuzsa M Szigeti, István Pócsi, György Trencsényi, Dezső Szikra, Ildikó Garai, Tamás Gáll, Zsolt Combi, János Kappelmayer, György Balla, József Balla |
| المصدر: | International Journal of Molecular Sciences, Vol 21, Iss 13, p 4746 (2020) |
| بيانات النشر: | MDPI AG, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | atherosclerosis, lipid peroxidation, inflammation, siderophore, apolipoprotein e knockout mouse, positron emission tomography, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Hemoglobin, heme and iron are implicated in the progression of atherosclerosis. Therefore, we investigated whether the hydrophobic fungal iron chelator siderophore, desferricoprogen (DFC) inhibits atherosclerosis. DFC reduced atherosclerotic plaque formation in ApoE−/− mice on an atherogenic diet. It lowered the plasma level of oxidized LDL (oxLDL) and inhibited lipid peroxidation in aortic roots. The elevated collagen/elastin content and enhanced expression of adhesion molecule VCAM-1 were decreased. DFC diminished oxidation of Low-density Lipoprotein (LDL) and plaque lipids catalyzed by heme or hemoglobin. Formation of foam cells, uptake of oxLDL by macrophages, upregulation of CD36 and increased expression of TNF-α were reduced by DFC in macrophages. TNF-triggered endothelial cell activation (vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecules (ICAMs), E-selectin) and increased adhesion of monocytes to endothelium were attenuated. The increased endothelial permeability and intracellular gap formation provoked by TNF-α was also prevented by DFC. DFC acted as a cytoprotectant in endothelial cells and macrophages challenged with a lethal dose of oxLDL and lowered the expression of stress-responsive heme oxygenase-1 as sublethal dose was employed. Saturation of desferrisiderophore with iron led to the loss of the beneficial effects. We demonstrated that DFC accumulated within the atheromas of the aorta in ApoE−/− mice. DFC represents a novel therapeutic approach to control the progression of atherosclerosis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/21/13/4746; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms21134746 |
| URL الوصول: | https://doaj.org/article/575fa6529a9e425fb57f24efb4a94d1a |
| رقم الأكسشن: | edsdoj.575fa6529a9e425fb57f24efb4a94d1a |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms21134746 |