Effects of nebivolol on endothelial gene expression during oxidative stress in human umbilical vein endothelial cells.

Abstract

The endothelium plays a key role in the development of atherogenesis and its inflammatory and proliferative status influences the progression of atherosclerosis. The aim of this study is to compare the effects of two beta blockers such as nebivolol and atenolol on gene expression in human umbilical vein endothelial cells (HUVECs) following an oxidant stimulus. HUVECs were incubated with nebivolol or atenolol (10 micromol/L) for 24 hours and oxidative stress was induced by the addition of oxidized (ox)-LDL. Ox-LDL upregulated adhesion molecules (ICAM-1, ICAM-2, ICAM-3, E-selectin, and P-selectin); proteins linked to inflammation (IL-6 and TNFalpha), thrombotic state (tissue factor, PAI-1 and uPA), hypertension such as endothelin-1 (ET-1), and vascular remodeling such as metalloproteinases (MMP-2, MMP-9) and protease inhibitor (TIMP-1). The exposure of HUVECs to nebivolol, but not to atenolol, reduced these genes upregulated by oxidative stress both in terms of protein and RNA expression. The known antioxidant properties of the third generation beta blocker nebivolol seem to account to the observed differences seen when compared to atenolol and support the specific potential protective role of this beta blocker on the expression of a number of genes involved in the initiation and progression of atherosclerosis.

• Authors: Ulisse Garbin, Anna Fratta Pasini, Chiara Stranieri, Stefania Manfro, Chiara Mozzini, Veronica Boccioletti, Andrea Pasini, Mattia Cominacini, Stefano Evangelista, Luciano Cominacini
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2008 Pg. 367590 ( 2008) ISSN: 1466-1861 [Electronic] United States
• PMID: 18437228 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• Benzopyrans
• Cell Adhesion Molecules
• E-Selectin
• Ethanolamines
• ICAM2 protein, human
• ICAM3 protein, human
• P-Selectin
• Nebivolol
• Intercellular Adhesion Molecule-1
• Atenolol

Topics

• Antigens, CD (genetics, metabolism)
• Atenolol (pharmacology)
• Benzopyrans (pharmacology)
• Cell Adhesion Molecules (genetics, metabolism)
• Cells, Cultured
• E-Selectin (genetics, metabolism)
• Endothelial Cells (cytology, drug effects, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Ethanolamines (pharmacology)
• Gene Expression (drug effects)
• Humans
• Intercellular Adhesion Molecule-1 (genetics, metabolism)
• Nebivolol
• Oligonucleotide Array Sequence Analysis
• Oxidative Stress (drug effects)
• P-Selectin (genetics, metabolism)
• Umbilical Veins (cytology)