Effects of nebivolol on endothelial gene expression during oxidative stress in human umbilical vein endothelial cells.
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.
Garbin
Ulisse
U
Internal Medicine D, Department of Biomedical and Surgical Sciences, University of Verona, 37126 Verona, Italy.
Fratta Pasini
Anna
A
Stranieri
Chiara
C
Manfro
Stefania
S
Mozzini
Chiara
C
Boccioletti
Veronica
V
Pasini
Andrea
A
Cominacini
Mattia
M
Evangelista
Stefano
S
Cominacini
Luciano
L
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001262:Atenolol / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004983:Ethanolamines / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D000068577:Nebivolol; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects*; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D015703:Antigens, CD; D001578:Benzopyrans; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D004983:Ethanolamines; C065289:ICAM2 protein, human; C483616:ICAM3 protein, human; D019007:P-Selectin; D000068577:Nebivolol; D018799:Intercellular Adhesion Molecule-1; D001262:Atenolol