title: Regulation and role of endogenously produced hydrogen sulfide in angiogenesis.
abstract: Recent studies have implicated endogenously produced H2S in the angiogenic process. On one hand, pharmacological inhibition and silencing of the enzymes involved in H2S synthesis attenuate the angiogenic properties of endothelial cells, including proliferation, migration and tube-like structure network formation. On the other hand, enhanced production of H2S by substrate supplementation or over-expression of H2S-producing enzymes leads to enhanced angiogenic responses in cultured endothelial cells. Importantly, H2S up-regulates expression of the key angiogenic factor vascular endothelial growth factor (VEGF) and contributes to the angiogenic signaling in response to VEGF. The signaling pathways mediating H2S-induced angiogenesis include mitogen-activated protein kinases, phosphoinositide-3 kinase, nitric oxide/cGMP-regulated cascades and ATP-sensitive potassium channels. Endogenously produced H2S has also been shown to facilitate neovascularization in prototypical model systems in vivo, and to contribute to wound healing, post-ischemic angiogenesis in the heart and other tissues, as well as in tumor angiogenesis. Targeting of H2S synthesizing enzymes might offer novel therapeutic opportunities for angiogenesis-related diseases.
authors: Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Greece, Greece; Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Greece.
authors: Antonia
authors: A
authors: Katsouda
authors: Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Greece, Greece.
authors: Sofia-Iris
authors: SI
authors: Bibli
authors: Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Greece.
authors: Anastasia
authors: A
authors: Pyriochou
authors: Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
authors: Csaba
authors: C
authors: Szabo
authors: Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Greece, Greece; Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Greece. Electronic address: apapapet@pharm.uoa.gr.
authors: Andreas
authors: A
authors: Papapetropoulos
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D006862:Hydrogen Sulfide