title: Significant deterioration of anti-atherogenic efficacy of nebivolol in a double (apolipoprotein E and endothelial nitric oxide synthase) knockout mouse model of atherosclerosis in comparison to single (apolipoprotein E) knockout model.
abstract: Anti-atherogenic action of nebivolol in apolipoprotein E (apoE)-single knockout mouse model can be explained by its beneficial effect on endothelium, especially on endothelial nitric oxide synthase (eNOS). We, therefore, decided to use apoE and eNOS-double knockout mouse model to confirm that mechanism of nebivolol beneficial action. In apoE-single knockout mice, lesion area measured by "cross-section" of aortic roots was 79,244 ± 6,143 μm(2) in the control group versus 65,347 ± 6,152 μm(2) in nebivolol-treated group (P<0.05). However, in apoE and eNOS-double knockout mice, lesion area measured by "cross-section" of aortic roots was 92,319 ± 8,876 μm(2) in the control group versus 98,609 ± 9,164 μm(2) in nebivolol-treated group (P>0.05). The comparison between apoE-single knockout mice and apoE & eNOS-double knockout mice without treatment also showed statistically significant difference: 81,232 ± 8,264 μm(2) versus 92,319 ± 8,876 μm(2) (P<0.05). This is the first report that describes the effect of nebivolol on atherogenesis in apoE and eNOS-double knockout mice, proving directly the necessity of the presence of eNOS in endothelium for nebivolol to show its an anti-atherogenic potency.
authors.affiliation: Chair of Pharmacology, Jagiellonian University School of Medicine, Cracow, Poland. mmjawien@cyf-kr.edu.pl.
authors.forename: K
authors.initials: K
authors.lastname: Kus
authors.forename: A
authors.initials: A
authors.lastname: Wisniewska
authors.forename: J
authors.initials: J
authors.lastname: Toton-Zuranska
authors.forename: R
authors.initials: R
authors.lastname: Olszanecki
authors.forename: J
authors.initials: J
authors.lastname: Jawien
authors.forename: R
authors.initials: R
authors.lastname: Korbut
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D018345:Mice, Knockout; D000068577:Nebivolol; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D001578:Benzopyrans; D004983:Ethanolamines; D014280:Triglycerides; D000068577:Nebivolol; D002784:Cholesterol; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse