Vascular lesions frequently arise as complication in patients diagnosed with diabetes mellitus (DM). Presently, percutaneous coronary intervention (PCI) and antithrombotic therapy serve as primary treatments. However, in-stent restenosis persists as a challenging clinical issue following PCI, lacking sustained and effective treatment. Linarin (LN) exhibits diverse pharmacological activities and is regarded as a potential drug for treating various diseases, including DM. But its specific role in restenosis after vascular injury in DM patients remains unclear. A rat model of diabetes-related restenosis was established to evaluate the role of LN on neointimal hyperplasia. Vascular smooth muscle cells (VSMCs) stimulated by high glucose (HG, 30 mM) underwent LN treatment. Additionally, an overexpression plasmid of A disintegrin and metalloproteinases (ADAM10) was constructed to transfect VSMCs. We employed CCK-8, Brdu, wound-healing scratch, and transwell migration assays to evaluate the proliferation and migration of VSMCs. Furthermore, western blot and immunofluorescence assays were utilized to investigate the expressions of ADAM10 and the downstream Notch signaling pathway in vivo and in vitro models. LN notably alleviated intimal hyperplasia after vascular injury in DM rats and reduced the protein expression of ADAM10, alongside its downstream Notch1 signaling pathway-related proteins (Notch1, NICD and Hes1) in rat carotid artery tissues. LN effectively suppressed the proliferation and migration of VSMCs induced by HG, downregulating the protein expression of ADAM10, Notch1, NICD and Hes1. Moreover, our findings indicated that ADAM10 overexpression significantly reversed LN's effects on proliferation, migration, and the expression of Notch1 signaling pathway-related proteins in HG-treated VSMCs. LN demonstrates potential therapeutic efficacy in addressing restenosis after diabetic-related vascular injury, with the ADAM10 mediated Notch signaling pathway playing a pivotal role.
Keyphrases
- signaling pathway
- vascular smooth muscle cells
- cell proliferation
- pi k akt
- percutaneous coronary intervention
- epithelial mesenchymal transition
- angiotensin ii
- newly diagnosed
- ejection fraction
- acute myocardial infarction
- type diabetes
- induced apoptosis
- atrial fibrillation
- coronary artery disease
- wound healing
- high glucose
- glycemic control
- acute coronary syndrome
- st elevation myocardial infarction
- escherichia coli
- cardiovascular disease
- antiplatelet therapy
- endothelial cells
- prognostic factors
- gene expression
- south africa
- risk assessment
- heart failure
- adipose tissue
- fluorescent probe
- patient reported outcomes
- climate change
- wastewater treatment
- transcription factor
- mesenchymal stem cells
- long non coding rna
- human health
- living cells
- aqueous solution
- smooth muscle
- binding protein