The anti-inflammatory effect of the β1-adrenergic receptor antagonist metoprolol on high glucose treated human microvascular retinal endothelial cells
| Autor: | Giovanni Giurdanella, Anna Longo, Alfio Distefano, Melania Olivieri, Martina Cristaldi, Alessia Cosentino, Aleksandra Agafonova, Nunzia Caporarello, Gabriella Lupo, Carmelina Daniela Anfuso |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cytosolic Epinephrine QH301-705.5 MAP Kinase Signaling System NF-E2-Related Factor 2 Human retinal endothelial cells (HREC) Interleukin-1beta Anti-Inflammatory Agents Down-Regulation Neovascularization Physiologic Phospholipases A2 Cytosolic Article Diabetic retinopathy (DR) Nuclear factor erythroid-2-related factor 2 (Nrf2) Retina Phospholipase A2 (PLA2) Kelch-like ECH-associated protein 1 (Keap1) Humans Biology (General) Phosphorylation Physiologic Neovascularization Cell Proliferation diabetic retinopathy (DR) human retinal endothelial cells (HREC) β-Adrenergic Receptor (β-AR) metoprolol nuclear factor erythroid-2-related factor 2 (Nrf2) Cell Nucleus Kelch-Like ECH-Associated Protein 1 Tumor Necrosis Factor-alpha Endothelial Cells General Medicine Adrenergic beta-1 Receptor Antagonists Protein Transport Phospholipases A2 Glucose Cyclooxygenase 2 Microvessels Reactive Oxygen Species Heme Oxygenase-1 Metoprolol |
| Zdroj: | Cells Cells, Vol 11, Iss 51, p 51 (2022) Cells; Volume 11; Issue 1; Pages: 51 |
| Popis: | Hyperglycemia-induced impairment of the blood-retinal barrier represents the main pathological event in diabetic retinopathy that is elicited by a reduced cellular response to an accumulation of reactive oxygen species (ROS) and increased inflammation. The purpose of the study was to evaluate whether the selective β1-adrenoreceptor (β1-AR) antagonist metoprolol could modulate the inflammatory response to hyperglycemic conditions. For this purpose, human retinal endothelial cells (HREC) were treated with normal (5 mM) or high glucose (25 mM, HG) in the presence of metoprolol (10 μM), epinephrine (1 μM), or both compounds. Metoprolol prevented both the HG-induced reduction of cell viability (MTT assays) and the modulation of the angiogenic potential of HREC (tube formation assays) reducing the TNF-α, IL-1β, and VEGF mRNA levels (qRT-PCR). Moreover, metoprolol prevented the increase in phospho-ERK1/2, phospho-cPLA2, COX2, and protein levels (Western blot) as well as counteracting the translocation of ERK1/2 and cPLA2 (high-content screening). Metoprolol reduced ROS accumulation in HG-stimulated HREC by activating the anti-oxidative cellular response mediated by the Keap1/Nrf2/HO-1 pathway. In conclusion, metoprolol exerted a dual effect on HG-stimulated HREC, decreasing the activation of the pro-inflammatory ERK1/2/cPLA2/COX2 axis, and counteracting ROS accumulation by activating the Keap1/Nrf2/HO-1 pathway. |
| Databáze: | OpenAIRE |
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