Bintepe Ç., Reel B., Sarıyer E., Ersoy N., Bağrıyanık H. A., Erdal Bağrıyanık Ş. E.
ATHEROSCLEROSIS, cilt.407, sa.120102, ss.143, 2025 (SCI-Expanded, Scopus)
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Yayın Türü:
Makale / Özet
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Cilt numarası:
407
Sayı:
120102
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Basım Tarihi:
2025
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Doi Numarası:
10.1016/j.atherosclerosis.2025.120102
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Dergi Adı:
ATHEROSCLEROSIS
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Derginin Tarandığı İndeksler:
Scopus, Science Citation Index Expanded (SCI-EXPANDED), BIOSIS, Chemical Abstracts Core, EMBASE
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Sayfa Sayıları:
ss.143
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Dokuz Eylül Üniversitesi Adresli:
Evet
Özet
Background and Aims: Netrin-1, a guide molecule plays a role in vascular smooth muscle cell proliferation, migration, and vascular remodeling by regulating various downstream signaling pathways. The alteration of serum netrin-1 levels in diabetic patients and its association with vascular complications due to diabetes have made netrin-1 a potential target. In our study, we aimed to investigate the effects of nebivolol which is a third-generation β-blocker on netrin-1-related signaling pathways in high glucose-induced human coronary artery smooth muscle cells (HCASMCs).
Methods: Primary HCASMCs (ATCC, USA) were treated with 30 mM glucose and/or 1.5 μM nebivolol. Untreated cells were named control and DMSO (dissolvent). Expressions of netrin-1, p-ERK, p-JNK, p-FAK, ERK, JNK, FAK, AKT, and E-Cad were examined by immunofluorescence staining in HCASMCs seeded on coverslips. DAPI staining was applied to ensure nucleus visibility. Imaging was performed by using a fluorescence microscope (Olympus CX41, USA). Staining intensity was measured in the images using the ImageJ software. Data were analyzed statistically using the One-way ANOVA test followed by Tukey's multiple comparisons test.
Results: The expression levels of netrin-1 (p<0.05), and phosphorized derives of the proteins of the downstream signaling pathway of netrin-1 including p-ERK (p<0.001), p-JNK (p<0.001), p-FAK (p<0.001) and p-AKT (p<0.001) decreased in the glucose group compared to the control groups and did not change in nebivolol groups. The expression levels of ERK (p<0.05), JNK (p<0.01, p<0.001), FAK (p<0.01, p<0.05), and AKT (p<0.01, p<0.05) significantly decreased in the glucose group compared to the control groups, but they increased prominently in the nebivolol groups. On the contrary, the expression level of E-cad, an epithelial adhesion protein augmented in the glucose group (p<0.05) but reduced in the nebivolol groups.
Conclusions: Nebivolol may help to prevent restenosis associated with coronary artery disease in diabetic patients by regulating downstream pathways of netrin-1.