Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases

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dc.creatorLe, Duong Q.
dc.creatorKuriakose, Aneetta E.
dc.creatorNguyen, Dat X.
dc.creatorNguyen, Kytai T.
dc.creatorAcharya, Suchismita
dc.date.accessioned2022-08-18T18:32:06Z
dc.date.available2022-08-18T18:32:06Z
dc.date.issued2017-08-18
dc.description.abstractNitric oxide (NO) has been known to promote physiological angiogenesis to treat peripheral arterial diseases (PAD) by increasing the vascular endothelial growth factor (VEGF) level in endothelial cells (ECs) and preventing platelet adherence and leukocyte chemotaxis. However, the ongoing ischemic event during peripheral ischemia produces superoxide and diminishes the NO bioavailability by forming toxic peroxynitrite anion. Here we disclose an efficacious hybrid molecule 4-(5-Amino-1,2,3-oxadiazol-3-yl)-2,2,6,6-tetramethyl-1-piperidinol (SA-2) containing both antioxidant and NO donor functionalities that provide a therapeutic level of NO necessary to promote angiogenesis and to protect ECs against hydrogen peroxide-induced oxidative stress. Compound SA-2 scavenged reactive oxygen species, inhibited proliferation and migration of smooth muscle cells (SMCs) and promoted the tube formation from ECs. Copolymer poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with SA-2 provided a sustained release of NO over days, improved aqueous stability in serum, protected ECs against oxidative stress, and enhanced angiogenesis under stress conditions as compared to that of the control in the in vitro matrigel tube formation assay. These results indicated the potential use of SA-2 nanoparticles as an alternative therapy to treat PAD.
dc.description.sponsorshipWe are thankful for the funding support of UNTHSC for providing start-up funding (S.A.) and to NIH HL118498 (K.T.N.).
dc.identifier.citationLe, D. Q., Kuriakose, A. E., Nguyen, D. X., Nguyen, K. T., & Acharya, S. (2017). Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases. Scientific reports, 7(1), 8692. https://doi.org/10.1038/s41598-017-08441-9
dc.identifier.issn2045-2322
dc.identifier.issue1
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31589
dc.identifier.volume7
dc.publisherSpringer Nature
dc.relation.urihttps://doi.org/10.1038/s41598-017-08441-9
dc.rights.holder© The Author(s) 2017
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientific Reports
dc.subject.meshBlood Vessels / drug effects
dc.subject.meshBlood Vessels / metabolism
dc.subject.meshCell Hypoxia / drug effects
dc.subject.meshCell Movement / drug effects
dc.subject.meshCell Proliferation / drug effects
dc.subject.meshCell Survival / drug effects
dc.subject.meshHuman Umbilical Vein Endothelial Cells / drug effects
dc.subject.meshHuman Umbilical Vein Endothelial Cells / metabolism
dc.subject.meshHumans
dc.subject.meshMyocytes, Smooth Muscle / drug effects
dc.subject.meshMyocytes, Smooth Muscle / metabolism
dc.subject.meshNanoparticles / chemistry
dc.subject.meshNanoparticles / ultrastructure
dc.subject.meshNeovascularization, Physiologic / drug effects
dc.subject.meshNitric Oxide Donors / chemistry
dc.subject.meshNitric Oxide Donors / pharmacology
dc.subject.meshNitric Oxide Donors / therapeutic use
dc.subject.meshOxidative Stress / drug effects
dc.subject.meshPeripheral Arterial Disease / drug therapy
dc.subject.meshPeripheral Arterial Disease / pathology
dc.titleHybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases
dc.typeArticle
dc.type.materialtext

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