Academic Journal
Overexpression of VEGFα as a biomarker of endothelial dysfunction in aortic tissue of α-GAL-Tg/KO mice and its upregulation in the serum of patients with Fabry’s disease
| العنوان: | Overexpression of VEGFα as a biomarker of endothelial dysfunction in aortic tissue of α-GAL-Tg/KO mice and its upregulation in the serum of patients with Fabry’s disease |
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| المؤلفون: | Lund, N., Wieboldt, H., Fischer, L., Muschol, N., Braun, F., Huber, T., Sorriento, D., Iaccarino, G., Müllerleile, K., Tahir, E., Adam, G., Kirchhof, P., Fabritz, L., Patten, M. |
| المساهمون: | Lund, N., Wieboldt, H., Fischer, L., Muschol, N., Braun, F., Huber, T., Sorriento, D., Iaccarino, G., Müllerleile, K., Tahir, E., Adam, G., Kirchhof, P., Fabritz, L., Patten, M. |
| سنة النشر: | 2024 |
| المجموعة: | IRIS Università degli Studi di Napoli Federico II |
| مصطلحات موضوعية: | Fabry’s disease, VEGF, angiogenic marker, angiostatin, aortic vessel, endothelial dysfunction, transgenic knockout model, vasculopathy |
| الوصف: | Introduction: Fabry's disease is an X-linked lysosomal storage disorder caused by reduced activity of α-galactosidase A (GAL), leading to premature death on account of renal, cardiac, and vascular organ failure. Accumulation of the GAL substrate globotriaosylceramide (Gb3) in endothelial and smooth muscle cells is associated with early vascular cell damage, suggesting endothelial dysfunction as a driver of cardiorenal organ failure. Here, we studied the vascular expression of the key angiogenic factors, VEGFα and its antagonist angiostatin, in Fabry α-GAL-Tg/KO mice and determined circulating VEGFα and angiostatin serum levels in patients with Fabry's disease and healthy controls. Methods: Cryopreserved aortic vessels from six α-GAL-Tg/KO and six wild-type (WT) mice were obtained and VEGFα and angiostatin levels were determined by performing Western blot analysis. VEGFα expression was visualized by an immunohistochemical staining of paraffin aortic rings. In addition, VEGFα and angiostatin serum levels were measured by using an enzyme-linked immunosorbent assay in 48 patients with genetically verified Fabry's disease (50% male) and 22 healthy controls and correlated with disease severity markers such as lyso-Gb3, albuminuria, NTproBNP, high-sensitive troponin T (hsTNT), and myocardial wall thickness. Results: It was found that there was a significant increase in VEGFα protein expression (1.66 ± 0.35 vs. 0.62 ± 0.16, p = 0.0009) and a decrease in angiostatin expression (0.024 ± 0.007 vs. 0.053 ± 0.02, p = 0.038) in aortic lysates from α-GAL-Tg/KO compared with that from WT mice. Immunohistochemical staining revealed an adventitial VEGFα signal in α-GAL-Tg/KO mice, whereas no VEGFα signal could be detected in WT mice aortas. No differences in aortic angiostatin expression between α-GAL-Tg/KO- and WT mice could be visualized. The serum levels of VEGFα were significantly upregulated in patients with Fabry's disease compared with that in healthy controls (708.5 ± 426.3 vs. 458.5 ± 181.5 pg/ml, p = 0.048) and ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | volume:11; journal:FRONTIERS IN CARDIOVASCULAR MEDICINE; https://hdl.handle.net/11588/959711; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85185246147 |
| DOI: | 10.3389/fcvm.2024.1355033 |
| الاتاحة: | https://hdl.handle.net/11588/959711 https://doi.org/10.3389/fcvm.2024.1355033 |
| رقم الانضمام: | edsbas.F13CE8F0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fcvm.2024.1355033 |
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