Evidence map›Paper›PMID 17823371›Full record

ArticleCirculation research2007

Impaired angiogenesis after hindlimb ischemia in type 2 diabetes mellitus: differential regulation of vascular endothelial growth factor receptor 1 and soluble vascular endothelial growth factor receptor 1.

Surovi Hazarika, Ayotunde O Dokun, Yongjun Li, Aleksander S Popel, Christopher D Kontos, Brian H Annex

2 registry-linked trialsAbstract read
PubMed Publisher
In one paragraph

Article in Circulation research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 135 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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.

NCT03883412 phase4recruitingstarted 2019, after this paper: background citation

Effect of Exercise and/or Liraglutide on Vascular Dysfunction and Insulin Sensitivity in Type 2 Diabetes ( ZQL007)

Ran2019Enrolled60Registered outcomes6Posted comparisons0ConditionsType2 DiabetesArmsExercise, liraglutide
Open the trial in the graph
NCT04575844 phase4recruitingstarted 2020, after this paper: background citation

Effects of Exercise and GLP-1 Agonism on Muscle Microvascular Perfusion and Insulin Action in Adults With Metabolic Syndrome

Ran2020Enrolled80Registered outcomes6Posted comparisons0ConditionsMetabolic SyndromeArmsExercise Training, liraglutide, Liraglutide + Exercise training
Open the trial in the graph
3 · Its place in the literature

Who cites it

135 citing papers in PubMed, 1 synthesis or guideline pooled it, 200 citations in OpenAlex.

  1. Pooled it
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  4. Review
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  6. Fluid Shear Stress-Regulated Vascular Remodeling: Past, Present, and Future.Arteriosclerosis, thrombosis, and vascular biology · 2025
    Review
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  11. Article
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75 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

6 authors at 1 institution in 1 country.

Surovi HazarikaDivision of Cardiology, Duke University and Durham VA Medical Center, Durham, NC 27710, USA.
Ayotunde O Dokun
Yongjun Li
Aleksander S Popel
Christopher D Kontos
Brian H Annex
Johns Hopkins University · US

Funding

Angiogenic Signals in Diabetic ComplicationsU01DK076136 · NIDDK · DUKE UNIVERSITY · PI COFFMAN, THOMAS M · 2006 to 2010
$1.6M
Systems Biology of Angiogenesis: from Molecules to TherapyR33HL088286 · NHLBI · UNIVERSITY OF VIRGINIA · PI ANNEX, BRIAN H · 2006 to 2008
$1.2M
NHLBI NIH HHS R33 HL088286NIDDK NIH HHS U01 DK 076136
6 · The paper itself

Abstract

Deficient angiogenesis after ischemia may contribute to worse outcomes of peripheral arterial disease in patients with diabetes mellitus (DM). Vascular endothelial growth factor (VEGF) and its receptors promote angiogenesis. We hypothesized that in peripheral arterial disease, maladaptive changes in VEGF ligand/receptor expression could account for impaired angiogenesis in DM. Skeletal muscle from diet-induced, type 2 diabetic (DM) and age-matched normal chow (NC)-fed mice was collected at baseline and 3 and 10 days after hindlimb ischemia and analyzed for expression of VEGF (n=10 per group), full-length VEGF receptor (VEGFR)-1, soluble VEGFR-1, and markers of downstream VEGF signaling (n=20 per group) using ELISA, reverse transcriptase-polymerase chain reaction, and Western blots. In the absence of ischemia, DM mice had increased VEGF (NC versus DM: 26.6+/-2.6 versus 53.5+/-8.8 pg/mg protein; P<0.05), decreased soluble and membrane-bound VEGFR-1 (NC versus DM: 1.44+/-0.30 versus 0.85+/-0.08 and 1.03+/-0.10 versus 0.72+/-0.10, respectively; P<0.05), decreased phospho-AKT/AKT and phospho-endothelial NO synthase/endothelial NO synthase (NC versus DM: 0.76+/-0.2 versus 0.38+/-0.1 and 0.36+/-0.06 versus 0.25+/-0.04, respectively; P<0.05), and no change in VEGFR-2. After ischemia, both DM and NC had comparable increases in VEGF-A. VEGFR-1 and soluble VEGFR-1 expression increased in both groups, but the fold increase was significantly greater in DM. These data demonstrate that soluble VEGFR-1, an angiogenesis inhibitor, is regulated in skeletal muscle by type 2 DM and ischemia. In the absence of ischemia, despite reductions in both soluble VEGFR-1 and VEGFR-1, VEGF ligand signaling is lower in DM compared with controls. After ischemia, maladaptive upregulation of these receptors further reduces the capacity of VEGF to induce an angiogenic response, which may provide a novel target for therapy.

Indexed as

AnimalsDiabetes Mellitus, Type 2Diabetic AngiopathiesDisease Models, AnimalGene ExpressionHindlimbIschemiaMaleMiceMice, Inbred C57BLNeovascularization, PathologicNitric OxideRegional Blood FlowRNA, MessengerSignal TransductionSolubilityNitric OxideRNA, MessengerVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1

Identifiers

PMID17823371
OpenAlexW2153461920

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

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 Socratic graph.