title: P1,P4-diadenosine 5'-tetraphosphate induced DNA synthesis in mechanically injured cultured endothelial cells.
abstract: Rapid re-endothelialization following balloon angioplasty can reduce restenosis by inhibiting smooth muscle cell migration and proliferation. However, formation of a neointima layer following angioplasty can be inhibited due to endothelial cell dysfunction and denudation. In a companion paper, it has been illustrated that mechanical loading causes a decrease in DNA synthesis in bovine aortic endothelial cells (BAECs) thus rendering them dysfunctional. The purpose of this study was to overcome BAEC dysfunction by incubation with pharmacological agents to increase DNA synthesis. Previous studies demonstrated that the adenosine dinucleotides Ap4A and Ap2A induced nitric oxide (NO) production from BAEC while Ap3A, Ap5A and Ap6A did not. This paper demonstrates that Ap4A and Ap2A induce a 1.46- and 1.16-fold increase in DNA synthesis in mechanically stressed BAECs respectively, while Ap3A, Ap5A and Ap6A do not. Additionally, NOC-18, a slow NO release NO donor, significantly increases DNA synthesis in mechanically stressed BAECs without affecting unloaded cells. These results are consistent with NO inducing DNA synthesis in mechanically stressed BAECs.
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, South Carolina, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Woodell
authors.forename: M
authors.initials: M
authors.lastname: LaBerge
authors.forename: E M
authors.initials: EM
authors.lastname: Langan
authors.forename: R H
authors.initials: RH
authors.lastname: Hilderman
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002417:Cattle; D048429:Cell Size / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D004247:DNA / Q000032:analysis / Q000096:biosynthesis*; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004548:Elasticity; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D040542:Mechanotransduction, Cellular / Q000187:drug effects*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology*; D011312:Pressure; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013314:Stress, Mechanical; D014226:Triazenes / Q000494:pharmacology
chemical_list: C114535:1-hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1-triazene; D003470:Culture Media; D015226:Dinucleoside Phosphates; C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D014226:Triazenes; C099612:NOC 9; C020733:diadenosine tetraphosphate; D004247:DNA