{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T06:09:44Z","timestamp":1779430184842,"version":"3.53.1"},"reference-count":62,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    Revascularization strategies and gene therapy for treatment of ischemic diseases remain to be fully optimized for use in human and veterinary clinical medicine. The continued evolution of such strategies must take into consideration two compounds, which act as critical effectors of angiogenesis by endothelial cells. Nevertheless, the nature of interaction between hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) and nitric oxide (NO) remained undefined at the time of this writing.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    The present study uses ZYZ-803, a novel synthetic H\n                    <jats:sub>2<\/jats:sub>\n                    S\u2013NO hybrid molecule, which, under physiological conditions, slowly decomposes to release H\n                    <jats:sub>2<\/jats:sub>\n                    S and NO. This is observed to dose dependently mediate cell proliferation, migration, and tube-like structure formation\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    along with increased angiogenesis in rat aortic rings, Matrigel plug\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    , and a murine ischemic hind limb model. The effects of ZYZ-803 exhibited significantly greater potency than those of H\n                    <jats:sub>2<\/jats:sub>\n                    S and\/or NO donor alone. The compound stimulated cystathionine\n                    <jats:italic toggle=\"yes\">\u03b3<\/jats:italic>\n                    -lyase (CSE) expression and endothelial NO synthase (eNOS) activity to produce H\n                    <jats:sub>2<\/jats:sub>\n                    S and NO. Blocking CSE and\/or eNOS suppressed both H\n                    <jats:sub>2<\/jats:sub>\n                    S and NO generation as well as the proangiogenic effect of ZYZ-803. Sirtuin-1 (SIRT1), CSE, and\/or eNOS small interfering RNA (siRNA) suppressed the angiogenic effect of ZYZ-803-induced SIRT1 expression, VEGF, and cyclic guanosine 5\u2032-monophosphate (cGMP) levels. These gasotransmitters cooperatively regulated angiogenesis through an SIRT1\/VEGF\/cGMP pathway.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation and Conclusion:<\/jats:italic>\n                    <\/jats:bold>\n                    H\n                    <jats:sub>2<\/jats:sub>\n                    S and NO exert mutual influence on biological functions mediated by both compounds. Functional convergence occurs in the SIRT1-dependent proangiogenic processes. These two gasotransmitters are mutually required for physiological regulation of endothelial homeostasis. These ongoing characterizations of mechanisms by which ZYZ-803 influences angiogenesis provide expanding insight into strategies for treatment of ischemic diseases.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    25, 498\u2013514.\n                  <\/jats:p>","DOI":"10.1089\/ars.2015.6607","type":"journal-article","created":{"date-parts":[[2016,5,12]],"date-time":"2016-05-12T22:33:33Z","timestamp":1463092413000},"page":"498-514","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":59,"title":["Novel Angiogenic Activity and Molecular Mechanisms of ZYZ-803, a Slow-Releasing Hydrogen Sulfide\u2013Nitric Oxide Hybrid Molecule"],"prefix":"10.1177","volume":"25","author":[{"given":"Qingxun","family":"Hu","sequence":"first","affiliation":[{"name":"Fudan University","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wu","sequence":"additional","affiliation":[{"name":"Fudan University","place":["China"]},{"name":"Tongji University School of 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