Cystathionine γ-lyase regulates arteriogenesis through NO-dependent monocyte recruitment

Gopi K. Kolluru, Shyamal C. Bir, Shuai Yuan, Xinggui Shen, Sibile Pardue, Rui Wang, Christopher G. Kevil

Research output: Contribution to journalArticle

Abstract

AIMS: 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.

METHODS AND 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.

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)590-600
Number of pages11
JournalCardiovascular Research
Volume107
Issue number4
DOIs
Publication statusPublished - 1 Sep 2015

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Bibliographical note

This is a pre-copyedited, author-produced PDF of an article accepted for publication in Cardiovascular Research following peer review. The version of record Kolluru, G. K., Bir, S. C., Yuan, S., Shen, X., Pardue, S., Wang, R., & Kevil, C. G. (2015). Cystathionine γ-lyase regulates arteriogenesis through NO-dependent monocyte recruitment. Cardiovascular Research, 107(4), 590-600, is available online at: http://dx.doi.org/10.1093/cvr/cvv198

Keywords

  • sulfides
  • cystathionine gamma-lyase
  • cytokines
  • animal disease models
  • hydrogen sulfide
  • ischemia
  • nitric oxide
  • inbred C57BL mice
  • knockout mice
  • monocytes
  • physiologic neovascularization

Cite this

Kolluru, G. K., Bir, S. C., Yuan, S., Shen, X., Pardue, S., Wang, R., & Kevil, C. G. (2015). Cystathionine γ-lyase regulates arteriogenesis through NO-dependent monocyte recruitment. Cardiovascular Research, 107(4), 590-600. https://doi.org/10.1093/cvr/cvv198