Evidence map›Paper›PMID 22517358›Full record

ArticleAmerican journal of physiology. Cell physiology2012

Increased endogenous H2S generation by CBS, CSE, and 3MST gene therapy improves ex vivo renovascular relaxation in hyperhomocysteinemia.

Utpal Sen, Pushpakumar B Sathnur, Sourav Kundu, Srikanth Givvimani, Denise M Coley, Paras K Mishra, Natia Qipshidze, Neetu Tyagi, Naira Metreveli, Suresh C Tyagi

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
6.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

70 citing papers in PubMed, 113 citations in OpenAlex.

  1. Significance of GSH and HRedox report : communications in free radical research · 2026
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  4. Therapeutic Gases in Biomedicine: Updates on Nitric Oxide and Beyond.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  5. Article
  6. CSE/HJournal of cachexia, sarcopenia and muscle · 2025
    Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. HCells · 2024
    Article
  13. Article
  14. Review
  15. Review
  16. The Triple Crown: NO, CO, and HPharmacology & therapeutics · 2023
    Review
  17. Role of Hydrogen Sulfide and Hypoxia in Hepatic Angiogenesis of Portal Hypertension.Journal of clinical and translational hepatology · 2023
    Review
  18. Clinical Potential of Hydrogen Sulfide in Peripheral Arterial Disease.International journal of molecular sciences · 2023
    Review
  19. Review
  20. Review

10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Utpal SenDepartment of Physiology and Biophysics, University of Louisville School of Medicine, Kentucky, USA. u0sen001@louisville.edu
Pushpakumar B Sathnur
Sourav Kundu
Srikanth Givvimani
Denise M Coley
Paras K Mishra
Natia Qipshidze
Neetu Tyagi
Naira Metreveli
Suresh C Tyagi
University of Louisville · US

Funding

Mechanism of Vascular Remodeling in HyperhomocysteinemiaR01HL071010 · NHLBI · UNIVERSITY OF MISSISSIPPI MEDICAL CENTER · PI TYAGI, SURESH C. · 2002 to 2010
$2.7M
Homocysteine & Angiotensin II in Renovascular RemodelingR01HL104103 · NHLBI · UNIVERSITY OF LOUISVILLE · PI SEN, UTPAL · 2011 to 2015
$1.8M
Implications of Endothelial-Myocyte Uncoupling in Cardiac ArrhythmiaR01HL088012 · NHLBI · UNIVERSITY OF LOUISVILLE · PI TYAGI, SURESH C. · 2007 to 2010
$1.5M
NHLBI NIH HHS HL-104103NHLBI NIH HHS HL-71010NHLBI NIH HHS HL-88012NHLBI NIH HHS R01 HL071010NHLBI NIH HHS R01 HL088012NHLBI NIH HHS R01 HL104103
6 · The paper itself

Abstract

Hydrogen sulfide (H(2)S) has recently been identified as a regulator of various physiological events, including vasodilation, angiogenesis, antiapoptotic, and cellular signaling. Endogenously, H(2)S is produced as a metabolite of homocysteine (Hcy) by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST). Although Hcy is recognized as vascular risk factor at an elevated level [hyperhomocysteinemia (HHcy)] and contributes to vascular injury leading to renovascular dysfunction, the exact mechanism is unclear. The goal of the current study was to investigate whether conversion of Hcy to H(2)S improves renovascular function. Ex vivo renal artery culture with CBS, CSE, and 3MST triple gene therapy generated more H(2)S in the presence of Hcy, and these arteries were more responsive to endothelial-dependent vasodilation compared with nontransfected arteries treated with high Hcy. Cross section of triple gene-delivered renal arteries immunostaining suggested increased expression of CD31 and VEGF and diminished expression of the antiangiogenic factor endostatin. In vitro endothelial cell culture demonstrated increased mitophagy during high levels of Hcy and was mitigated by triple gene delivery. Also, dephosphorylated Akt and phosphorylated FoxO3 in HHcy were reversed by H(2)S or triple gene delivery. Upregulated matrix metalloproteinases-13 and downregulated tissue inhibitor of metalloproteinase-1 in HHcy were normalized by overexpression of triple genes. Together, these results suggest that H(2)S plays a key role in renovasculopathy during HHcy and is mediated through Akt/FoxO3 pathways. We conclude that conversion of Hcy to H(2)S by CBS, CSE, or 3MST triple gene therapy improves renovascular function in HHcy.

Indexed as

Genetic TherapyAnimalsCells, CulturedCystathionine beta-SynthaseCystathionine gamma-LyaseEndostatinsForkhead Box Protein O3Forkhead Transcription FactorsHomocysteineHydrogen SulfideHyperhomocysteinemiaHypertension, RenovascularMatrix Metalloproteinase 13MiceMice, Inbred C57BLOrgan Culture Techniques3-mercaptopyruvate sulphurtransferaseCystathionine beta-SynthaseCystathionine gamma-LyaseEndostatinsForkhead Box Protein O3Forkhead Transcription FactorsFoxO3 protein, mouseHomocysteineHydrogen SulfideMatrix Metalloproteinase 13Platelet Endothelial Cell Adhesion Molecule-1Proto-Oncogene Proteins c-aktReactive Oxygen SpeciesSulfurtransferasesTissue Inhibitor of Metalloproteinase-1Vascular Endothelial Growth Factor A

Identifiers

PMID22517358
PMCPMC3404527
OpenAlexW2139451085

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.