PMID- 30175474
OWN - NLM
STAT- MEDLINE
DCOM- 20190910
LR  - 20230928
IS  - 2051-817X (Electronic)
IS  - 2051-817X (Linking)
VI  - 6
IP  - 17
DP  - 2018 Sep
TI  - Hydrogen sulfide improves postischemic neoangiogenesis in the hind limb of 
      cystathionine-beta-synthase mutant mice via PPAR-gamma/VEGF axis.
PG  - e13858
LID - 10.14814/phy2.13858 [doi]
LID - e13858
AB  - Neoangiogenesis is a fundamental process which helps to meet energy requirements, 
      tissue growth, and wound healing. Although previous studies showed that 
      Peroxisome proliferator-activated receptor (PPAR-gamma) regulates neoangiogenesis via 
      upregulation of vascular endothelial growth factor (VEGF), and both VEGF and 
      PPAR-gamma expressions were inhibited during hyperhomocysteinemic (HHcy), whether 
      these two processes could trigger pathological effects in skeletal muscle via 
      compromising neoangiogenesis has not been studied yet. Unfortunately, there are 
      no treatment options available to date for ameliorating HHcy-mediated 
      neoangiogenic defects. Hydrogen sulfide (H(2) S) is a novel gasotransmitter that 
      can induce PPAR-gamma levels. However, patients with cystathionine-beta-synthase (CBS) 
      mutation(s) cannot produce a sufficient amount of H(2) S. We hypothesized that 
      exogenous supplementation of H(2) S might improve HHcy-mediated poor 
      neoangiogenesis via the PPAR-gamma/VEGF axis. To examine this, we created a hind limb 
      femoral artery ligation (FAL) in CBS(+/-) mouse model and treated them with 
      GYY4137 (a long-acting H(2) S donor compound) for 21 days. To evaluate 
      neoangiogenesis, we used barium sulfate angiography and laser Doppler blood flow 
      measurements in the ischemic hind limbs of experimental mice post-FAL to assess 
      blood flow. Proteins and mRNAs levels were studied by Western blots and qPCR 
      analyses. HIF1-alpha, VEGF, PPAR-gamma and p-eNOS expressions were attenuated in skeletal 
      muscle of CBS(+/-) mice after 21 days of FAL in comparison to wild-type (WT) 
      mice, that were improved via GYY4137 treatment. We also found that the collateral 
      vessel density and blood flow were significantly reduced in post-FAL CBS(+/-) 
      mice compared to WT mice and these effects were ameliorated by GYY4137. Moreover, 
      we found that plasma nitrite levels were decreased in post-FAL CBS(+/-) mice 
      compared to WT mice, which were mitigated by GYY4137 supplementation. These 
      results suggest that HHcy can inhibit neoangiogenesis via antagonizing the 
      angiogenic signal pathways encompassing PPAR-gamma/VEGF axis and that GYY4137 could 
      serve as a potential therapeutic to alleviate the harmful metabolic effects of 
      HHcy conditions.
CI  - (c) 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on 
      behalf of The Physiological Society and the American Physiological Society.
FAU - Majumder, Avisek
AU  - Majumder A
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, Kentucky, 40202, USA.
AD  - Department of Biochemistry and Molecular Genetics, University of Louisville 
      School of Medicine, Louisville, Kentucky, 40202, USA.
FAU - Singh, Mahavir
AU  - Singh M
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, Kentucky, 40202, USA.
FAU - George, Akash K
AU  - George AK
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, Kentucky, 40202, USA.
FAU - Behera, Jyotirmaya
AU  - Behera J
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, Kentucky, 40202, USA.
FAU - Tyagi, Neetu
AU  - Tyagi N
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, Kentucky, 40202, USA.
FAU - Tyagi, Suresh C
AU  - Tyagi SC
AD  - Department of Physiology, University of Louisville School of Medicine, 
      Louisville, Kentucky, 40202, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Physiol Rep
JT  - Physiological reports
JID - 101607800
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (PPAR gamma)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Animals
MH  - Cystathionine beta-Synthase/*deficiency/genetics
MH  - Hindlimb/blood supply
MH  - Hydrogen Sulfide/*pharmacology/therapeutic use
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Ischemia/*drug therapy/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Muscle, Skeletal/*blood supply/metabolism
MH  - Mutation
MH  - Neovascularization, Physiologic/*drug effects
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - PPAR gamma/metabolism
MH  - *Signal Transduction
MH  - Vascular Endothelial Growth Factor A/metabolism
PMC - PMC6119702
OTO - NOTNLM
OT  - Angiogenesis
OT  - hydrogen sulfide
OT  - stress response
EDAT- 2018/09/04 06:00
MHDA- 2019/09/11 06:00
PMCR- 2018/09/02
CRDT- 2018/09/04 06:00
PHST- 2018/05/05 00:00 [received]
PHST- 2018/08/10 00:00 [revised]
PHST- 2018/08/13 00:00 [accepted]
PHST- 2018/09/04 06:00 [entrez]
PHST- 2018/09/04 06:00 [pubmed]
PHST- 2019/09/11 06:00 [medline]
PHST- 2018/09/02 00:00 [pmc-release]
AID - PHY213858 [pii]
AID - 10.14814/phy2.13858 [doi]
PST - ppublish
SO  - Physiol Rep. 2018 Sep;6(17):e13858. doi: 10.14814/phy2.13858.