Nitric oxide releasing nanofiber stimulates revascularization in response to ischemia via cGMP-dependent protein kinase.
Autor: | Lee KH; Department of Internal Medicine, Division of Cardiovascular, Kyung Hee University Hospital, Kyung Hee University, Seoul, Korea.; Department of Biotechnology, Cha University, Pocheon, Korea., Song MY; Department of Internal Medicine, Division of Cardiovascular, Kyung Hee University Hospital, Kyung Hee University, Seoul, Korea., Lee S; Department of Internal Medicine, Division of Cardiovascular, Kyung Hee University Hospital, Kyung Hee University, Seoul, Korea., Park J; Department of Internal Medicine, Division of Cardiovascular, Kyung Hee University Hospital, Kyung Hee University, Seoul, Korea.; Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea., Kang JH; Department of Internal Medicine, Division of Cardiovascular, Kyung Hee University Hospital, Kyung Hee University, Seoul, Korea., Cho H; Department of Internal Medicine, Division of Cardiovascular, Kyung Hee University Hospital, Kyung Hee University, Seoul, Korea., Kim KB; Department of Chemistry, Kwangwoon University, Seoul, Korea., Son SJ; Department of Chemistry, Kwangwoon University, Seoul, Korea., Cheng XW; Department of Internal Medicine, Division of Cardiovascular, Kyung Hee University Hospital, Kyung Hee University, Seoul, Korea.; Department of Cardiology and Hypertension, Jilin Provincial Key Laboratory of Stress and Cardiovascular Diseas, Yanbian University Hospital, Yanji, China., Lee YJ; Department of Biomedical Engineering, College of Medicine, Kyung Hee University, Seoul, Korea., Lee GJ; Department of Biomedical Engineering, College of Medicine, Kyung Hee University, Seoul, Korea., Shin JH; Department of Chemistry, Kwangwoon University, Seoul, Korea., Kim W; Department of Internal Medicine, Division of Cardiovascular, Kyung Hee University Hospital, Kyung Hee University, Seoul, Korea. |
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Jazyk: | angličtina |
Zdroj: | PloS one [PLoS One] 2024 May 20; Vol. 19 (5), pp. e0303758. Date of Electronic Publication: 2024 May 20 (Print Publication: 2024). |
DOI: | 10.1371/journal.pone.0303758 |
Abstrakt: | Nitric oxide (NO) promotes angiogenesis via various mechanisms; however, the effective transmission of NO in ischemic diseases is unclear. Herein, we tested whether NO-releasing nanofibers modulate therapeutic angiogenesis in an animal hindlimb ischemia model. Male wild-type C57BL/6 mice with surgically-induced hindlimb ischemia were treated with NO-releasing 3-methylaminopropyltrimethoxysilane (MAP3)-derived or control (i.e., non-NO-releasing) nanofibers, by applying them to the wound for 20 min, three times every two days. The amount of NO from the nanofiber into tissues was assessed by NO fluorometric assay. The activity of cGMP-dependent protein kinase (PKG) was determined by western blot analysis. Perfusion ratios were measured 2, 4, and 14 days after inducing ischemia using laser doppler imaging. On day 4, Immunohistochemistry (IHC) with F4/80 and gelatin zymography were performed. IHC with CD31 was performed on day 14. To determine the angiogenic potential of NO-releasing nanofibers, aorta-ring explants were treated with MAP3 or control fiber for 20 min, and the sprout lengths were examined after 6 days. As per either LDPI (Laser doppler perfusion image) ratio or CD31 capillary density measurement, angiogenesis in the ischemic hindlimb was improved in the MAP3 nanofiber group; further, the total nitrate/nitrite concentration in the adduct muscle increased. The number of macrophage infiltrations and matrix metalloproteinase-9 (MMP-9) activity decreased. Vasodilator-stimulated phosphoprotein (VASP), one of the major substrates for PKG, increased phosphorylation in the MAP3 group. MAP3 nanofiber or NO donor SNAP (s-nitroso-n-acetyl penicillamine)-treated aortic explants showed enhanced sprouting in an ex vivo aortic ring assay, which was partially abrogated by KT5823, a potent inhibitor of PKG. These findings suggest that the novel NO-releasing nanofiber, MAP3 activates PKG and promotes therapeutic angiogenesis in response to hindlimb ischemia. (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) |
Databáze: | MEDLINE |
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