Evidence map›Paper›PMID 21653942›Full record

ArticleBlood2011

Hyperhomocysteinemia impairs endothelium-derived hyperpolarizing factor-mediated vasorelaxation in transgenic cystathionine beta synthase-deficient mice.

Zhongjian Cheng, Xiaohua Jiang, Warren D Kruger, Domenico Praticò, Sapna Gupta, Karthik Mallilankaraman, Muniswamy Madesh, Andrew I Schafer, William Durante, Xiaofeng Yang and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

39 citing papers in PubMed, 69 citations in OpenAlex.

  1. Article
  2. Article
  3. Homocysteine Attack on Vascular Endothelium-Old and New Features.International journal of molecular sciences · 2025
    Review
  4. Redox Regulation of KAntioxidants & redox signaling · 2024
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Ly6CArteriosclerosis, thrombosis, and vascular biology · 2019
    Article
  15. Article
  16. Article
  17. Cystathionine β-synthase deficiency: Of mice and men.Molecular genetics and metabolism · 2017
    Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 2 countries.

Zhongjian ChengDepartment of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Xiaohua Jiang
Warren D Kruger
Domenico Praticò
Sapna Gupta
Karthik Mallilankaraman
Muniswamy Madesh
Andrew I Schafer
William Durante
Xiaofeng Yang
Hong Wang
Cardiovascular Research Center · BRFox Chase Cancer Center · USTemple University · USCornell University · USUniversity of Missouri · US

Funding

Coordination of Pathophysiologic Endothelial Cell Signaling by ROSR01HL086699 · NHLBI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI MUNISWAMY, MADESH · 2008 to 2018
$4.3M
Atherogenic mechanisms with homocysteineR01HL077288 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2004 to 2014
$3.8M
GENETIC MODULATION OF CBS TO LOWER PLASMA HOMOCYSTEINER01HL057299 · NHLBI · FOX CHASE CANCER CENTER · PI KRUGER, WARREN D · 2001 to 2009
$3.2M
Inhibition of Endothelial Growth by HomocysteineR01HL067033 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2002 to 2011
$3.0M
Suppression of vascular endothelial cell inflammationR01HL094451 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI YANG, XIAOFENG · 2009 to 2013
$1.8M
Role of HHcy in diabetic vascular diseaseR01HL082774 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI WANG, HONG · 2006 to 2010
$1.8M
ARGINASE AND ARTERIAL INJURYR01HL074966 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI DURANTE, WILLIAM · 2005 to 2009
$1.6M
RISK OF VASCULAR DISEASE IN CBS HETEROZYGOTESR29HL057299 · NHLBI · FOX CHASE CANCER CENTER · PI KRUGER, WARREN D · 1997 to 2000
$66k
NHLBI NIH HHS HL57299NHLBI NIH HHS HL67033NHLBI NIH HHS HL74966NHLBI NIH HHS HL77288NHLBI NIH HHS HL82774NHLBI NIH HHS HL86699NHLBI NIH HHS HL94451NHLBI NIH HHS R01 HL057299NHLBI NIH HHS R01 HL067033NHLBI NIH HHS R01 HL074966NHLBI NIH HHS R01 HL077288NHLBI NIH HHS R01 HL082774NHLBI NIH HHS R01 HL086699NHLBI NIH HHS R01 HL094451NHLBI NIH HHS R29 HL057299PHS HHS SLORR27327
6 · The paper itself

Abstract

Hyperhomocysteinemia (HHcy) is associated with endothelial dysfunction (ED), but the mechanism is largely unknown. In this study, we investigated the role and mechanism of HHcy-induced ED in microvasculature in our newly established mouse model of severe HHcy (plasma total homocysteine, 169.5 μM). We found that severe HHcy impaired nitric oxide (NO)- and endothelium-derived hyperpolarizing factor (EDHF)-mediated, endothelium-dependent relaxations of small mesenteric arteries (SMAs). Endothelium-independent and prostacyclin-mediated endothelium-dependent relaxations were not changed. A nonselective Ca(2+)-activated potassium channel (K(Ca)) inhibitor completely blocked EDHF-mediated relaxation. Selective blockers for small-conductance K(Ca) (SK) or intermediate-conductance K(Ca) (IK) failed to inhibit EDHF-mediated relaxation in HHcy mice. HHcy increased the levels of SK3 and IK1 protein, superoxide (O(2)(-)), and 3-nitrotyrosine in the endothelium of SMAs. Preincubation with antioxidants and peroxynitrite (ONOO(-)) inhibitors improved endothelium-dependent and EDHF-mediated relaxations and decreased O(2)(-) production in SMAs from HHcy mice. Further, EDHF-mediated relaxation was inhibited by ONOO(-) and prevented by catalase in the control mice. Finally, L-homocysteine stimulated O(2)(-) production, which was reversed by antioxidants, and increased SK/IK protein levels and tyrosine nitration in cultured human cardiac microvascular endothelial cells. Our results suggest that HHcy impairs EDHF relaxation in SMAs by inhibiting SK/IK activities via oxidation- and tyrosine nitration-related mechanisms.

Indexed as

VasodilationAnimalsBiological FactorsCardiovascular DiseasesCell LineCystathionine beta-SynthaseGene DeletionHomocysteineHumansHyperhomocysteinemiaMesenteric ArteriesMiceMice, TransgenicNitrogen OxidesBiological FactorsCystathionine beta-Synthaseendothelium-dependent hyperpolarization factorHomocysteineNitrogen Oxides

Identifiers

PMID21653942
PMCPMC3158725
OpenAlexW2031958116

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.