title: Cystathionine γ-lyase regulates arteriogenesis through NO-dependent monocyte recruitment.
abstract: OBJECTIVE
  Hydrogen sulfide (H2S) is a vasoactive gasotransmitter that is endogenously produced in the vasculature by the enzyme cystathionine γ-lyase (CSE). However, the importance of CSE activity and local H2S generation for ischaemic vascular remodelling remains completely unknown. In this study, we examine the hypothesis that CSE critically regulates ischaemic vascular remodelling involving H2S-dependent mononuclear cell regulation of arteriogenesis.
  
  
  RESULTS
  Arteriogenesis including mature vessel density, collateral formation, blood flow, and SPY angiographic blush rate were determined in wild-type (WT) and CSE knockout (KO) mice at different time points following femoral artery ligation (FAL). The role of endogenous H2S in regulation of IL-16 expression and subsequent recruitment of monocytes, and expression of VEGF and bFGF in ischaemic tissues, were determined along with endothelial progenitor cell (CD34/Flk1) formation and function. FAL of WT mice significantly increased CSE activity, expression and endogenous H2S generation in ischaemic tissues, and monocyte infiltration, which was absent in CSE-deficient mice. Treatment of CSE KO mice with the polysulfide donor diallyl trisulfide restored ischaemic vascular remodelling, monocyte infiltration, and cytokine expression. Importantly, exogenous H2S therapy restored nitric oxide (NO) bioavailability in CSE KO mice that was responsible for monocyte recruitment and arteriogenesis.
  
  
  CONCLUSIONS
  Endogenous CSE/H2S regulates ischaemic vascular remodelling mediated during hind limb ischaemia through NO-dependent monocyte recruitment and cytokine induction revealing a previously unknown mechanism of arteriogenesis.
authors.affiliation: Department of Pathology, LSU Health Sciences Center Shreveport Center for Cardiovascular Diseases and Sciences, LSU Health Sciences Center Shreveport, 1501 Kings Hwy, Shreveport, LA 71130, USA.
authors.forename: Gopi K
authors.initials: GK
authors.lastname: Kolluru
authors.affiliation: Department of Pathology, LSU Health Sciences Center Shreveport.
authors.forename: Shyamal C
authors.initials: SC
authors.lastname: Bir
authors.affiliation: Department of Pathology, LSU Health Sciences Center Shreveport Center for Cardiovascular Diseases and Sciences, LSU Health Sciences Center Shreveport, 1501 Kings Hwy, Shreveport, LA 71130, USA.
authors.forename: Shuai
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Department of Pathology, LSU Health Sciences Center Shreveport.
authors.forename: Xinggui
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Pathology, LSU Health Sciences Center Shreveport.
authors.forename: Sibile
authors.initials: S
authors.lastname: Pardue
authors.affiliation: Department of Biology, Lakehead University, Thunder Bay, ON, Canada.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Pathology, LSU Health Sciences Center Shreveport Center for Cardiovascular Diseases and Sciences, LSU Health Sciences Center Shreveport, 1501 Kings Hwy, Shreveport, LA 71130, USA ckevil@lsuhsc.edu.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kevil
mesh_terms: D000818:Animals; D003542:Cystathionine gamma-Lyase / Q000235:genetics* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000378:metabolism*; D013440:Sulfides / Q000378:metabolism
chemical_list: D016207:Cytokines; D013440:Sulfides; D009569:Nitric Oxide; C032915:polysulfide; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
keywords: Arteriogenesis; Cystathionine γ-lyase; Hydrogen sulfide; Ischaemia; Nitric oxide; Vascular remodelling