Statins suppress glucose-induced plasminogen activator inhibitor-1 expression by regulating RhoA and nuclear factor-κB activities in cardiac microvascular endothelial cells
| Autor: | Ning-Hua Yao, Xiang-Jun Yang, Xiao-Qing Ni, Juan Qian, Jian-Hua Zhu |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
RHOA Statin Geranylgeranyl pyrophosphate medicine.drug_class Blotting Western Farnesyl pyrophosphate Enzyme-Linked Immunosorbent Assay Real-Time Polymerase Chain Reaction General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley chemistry.chemical_compound Plasminogen Activator Inhibitor 1 medicine Animals Electrophoretic mobility shift assay Cells Cultured biology Gene Expression Profiling NF-kappa B Endothelial Cells Molecular biology Rats IκBα Glucose chemistry Gene Expression Regulation Plasminogen activator inhibitor-1 biology.protein Hydroxymethylglutaryl-CoA Reductase Inhibitors rhoA GTP-Binding Protein Plasminogen activator |
| Zdroj: | Experimental biology and medicine (Maywood, N.J.). 238(1) |
| ISSN: | 1535-3699 |
| Popis: | The aim of this study was to investigate the possible proinflammatory signaling pathways involved in statin inhibition of glucose-induced plasminogen activator inhibitor-1 (PAI-1) expression in cardiac microvascular endothelial cells (CMECs). Primary rat CMECs were grown in the presence of 5.7 or 23 mmol/L glucose. PAI-1 mRNA and protein expression levels were measured by realtime polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay, respectively. A pull-down assay was performed to determine RhoA activity. IkBa protein expression was measured by Western blotting, nuclear factor (NF)-kB activation was detected by electrophoretic mobility shift assay and its transcription activity was determined by a dual luciferase reporter gene assay. PAI-1 mRNA and protein expression levels were both increased with high glucose concentrations, but they were significantly suppressed by simvastatin and atorvastatin treatment (P, 0.01) and the effects were reversed by mevalonate (100 mmol/L) and geranylgeranyl pyrophosphate (10 μmol/L) but not farnesyl pyrophosphate (10 μmol/L). Such effects were similar to those of a RhoA inhibitor, C3 exoenzyme (5 μg/mL), inhibitors of RhoA kinase (ROCK), Y-27632 (10 μmol/L) and hydroxyfasudil (10 μmol/L) and an NF-kB inhibitor, BAY 11-7082 (5mmol/L). High glucose-induced RhoA and NF-kB activations in CMECs were both significantly inhibited by statins (P, 0.01). Simvastatin and atorvastatin equally suppress high glucose-induced PAI-1 expression. These effects of statins may occur partly by regulating the RhoA/ROCK-NF-kB pathway. The multifunctional roles of statins may be particularly beneficial for patients with metabolic syndrome. |
| Databáze: | OpenAIRE |
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