Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases
| Autor: | Kytai T. Nguyen, Suchismita Acharya, Dat X. Nguyen, Duong Le, Aneetta E. Kuriakose |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Angiogenesis Cell Survival Science Myocytes Smooth Muscle Neovascularization Physiologic 030204 cardiovascular system & hematology Pharmacology medicine.disease_cause Article Nitric oxide 03 medical and health sciences chemistry.chemical_compound Peripheral Arterial Disease 0302 clinical medicine Cell Movement medicine Human Umbilical Vein Endothelial Cells Humans Nitric Oxide Donors Cell Proliferation chemistry.chemical_classification Tube formation Reactive oxygen species Multidisciplinary Cell Hypoxia Vascular endothelial growth factor Oxidative Stress 030104 developmental biology chemistry Biochemistry Medicine Blood Vessels Nanoparticles Peroxynitrite Leukocyte chemotaxis Oxidative stress |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
| ISSN: | 2045-2322 |
| Popis: | Nitric 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. |
| Databáze: | OpenAIRE |
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