Major differences in gene expression in human coronary smooth muscle cells after nebivolol or metoprolol treatment.
OBJECTIVE
Vascular smooth muscle cells play a pivotal role in all stages of atherogenesis. Targeting their inflammatory and proliferative qualities might therefore inhibit the progression of atherosclerosis. This study aimed to characterize and compare the effects of the beta-receptor antagonists nebivolol and metoprolol on gene expression in human coronary artery smooth muscle cells (hcaSMC).


RESULTS
hcaSMC were incubated with nebivolol or metoprolol (10(-5) mol/l) for 72 h. The downregulated genes are involved in inflammatory processes, oxidative stress and smooth muscle cell proliferation: i.e. downregulated were by nebivolol: interleukin-1alpha, cyclooxygenase-2, tumor-necrosis-factor (TNF)-alpha-induced protein 6, PDGF-A, growth-related oncogenes 2 and 3. Metoprolol increased the expression of interleukin-1alpha, cyclooxygenase-1, TNF-alpha-induced protein 3, heme oxygenase 1 and granulocyte/macrophage-colony-stimulating factor. In addition downregulated was monocyte chemoattractant protein 1 (MCP-1) mRNA by nebivolol. Nebivolol (10(-5) mol/l) reduced the amount of basal NF-kappaB after 48 and 52 h but not metoprolol. In the culture supernatants, MCP-1 concentrations were reduced by nebivolol.


CONCLUSIONS
Nebivolol induced changes in the expression of inflammatory mediators in hcaSMC. These results add to data that suggest specific anti-inflammatory qualities of a beta-blocker of the third generation in comparison to metoprolol.
Wolf
Sabine C
SC
Medical Clinic IV, Department of Hypertension and Renal Failure, Eberhard-Karls-University, Tübingen, Germany. bernhard.brehm@onlinehome.de
Sauter
Gabriele
G
Jobst
Jürgen
J
Kempf
Volkard A
VA
Risler
Teut
T
Brehm
Bernhard R
BR
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D049109:Cell Proliferation; D003324:Coronary Artery Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D008790:Metoprolol / Q000494:pharmacology*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D000068577:Nebivolol; D018384:Oxidative Stress / Q000235:genetics; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D018836:Inflammation Mediators; D000068577:Nebivolol; D008790:Metoprolol