Effects of Nebivolol on Netrin-1 and Related Pathways in High Glucose-Induced Human Coronary Artery Smooth Muscle Cell Culture
Project no. 23304 · Status: Kapanmış (Yayın bekleniyor) · 2022
Summary
<p>Vascular damage and inflammatory processes that develop due to chronic hyperglycemia in diabetic patients cause vascular smooth muscle (VSM) cell proliferation/migration and intimal hyperplasia. Vascular damage then progresses to stenosis leading to myocardial infarction.</p><p>Netrin-1 is a member of a family of proteins identified as guide molecules. It is known that Netrin-1 facilitates atherosclerosis by stimulating VSM cell proliferation, migration and vascular remodeling. It has been reported that serum netrin-1 levels of patients with diabetes are high and show a positive correlation with diabetes-related vascular complications. Binding of netrin-1 to its specific receptors induces activation of MAPK, PKC, SRC, PI3 kinase and FAK signaling pathways. Its involvement in vascular damage, inflammation, atherosclerosis and stenosis/restenosis through activation of these pathways has made netrin-1 a potential target.</p><p>Nebivolol, a third-generation cardioselective beta blocker, has been shown to have antiproliferative, anti-inflammatory, antioxidant, antiplatelet and post-MI protective properties. However, its effects in the human coronary artery smooth muscle (HCASM) cell line and/or human diabetes injury model have not yet been examined. Additionally, the effects of nebivolol on netrin-1 and related signaling pathways are unknown. With this information, our study aimed to investigate the effects of nebivolol on netrin-1-related signaling pathways in HCASM cells induced by high glucose.</p><p>Demonstrating the possible beneficial effects of nebivolol on netrin-1 and related pathways in an experimental diabetic injury model may contribute to the prevention of conorary artery disease (CAD)-related stenosis/restenosis in diabetic patients with nebivolol treatment and to the understanding of the molecular mechanisms of the drug.</p>