Evidence map›Paper›PMID 20972335›Full record

ArticleThe Journal of clinical investigation2010

Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-α isoforms and promotes angiogenesis.

Goutam Ghosh, Indira V Subramanian, Neeta Adhikari, Xiaoxiao Zhang, Hemant P Joshi, David Basi, Y S Chandrashekhar, Jennifer L Hall, Sabita Roy, Yan Zeng and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 241 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
241citing papers in PubMed, 1 pooled it
13.7field-weighted citation impact, top 1% 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

241 citing papers in PubMed, 1 synthesis or guideline pooled it, 416 citations in OpenAlex.

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  7. A Multi-Tissue Yak (Animals : an open access journal from MDPI · 2026
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181 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Goutam GhoshDepartment of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Indira V Subramanian
Neeta Adhikari
Xiaoxiao Zhang
Hemant P Joshi
David Basi
Y S Chandrashekhar
Jennifer L Hall
Sabita Roy
Yan Zeng
Sundaram Ramakrishnan
University of Minnesota · USInstitute of Cardiology · PLUnited States Department of Veterans Affairs · US

Funding

Subcellular Targeting/Packaging of Opioids/ReceptorsP50DA011806 · NIDA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI LOH, HORACE · 1998 to 2012
$14.0M
TRAINING-PULMONARY CELL &MOLECULAR BIOLOGY &PHYSIOLOGYT32HL007741 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI DUDLEY, R. ADAMS, INGBAR, DAVID H · 1994 to 2023
$13.9M
Opioid Abuse, opportunistic infection and NeuroAIDSR01DA012104 · NIDA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI ROY, SABITA · 1999 to 2013
$3.7M
The Role of Heparan Sulfate in Vascular RemodelingR01HL081715 · NHLBI · UNIVERSITY OF MINNESOTA · PI HALL, JENNIFER L · 2007 to 2011
$1.9M
Morphine, HIV proteins, wound healing and InfectionR01DA022935 · NIDA · UNIVERSITY OF MINNESOTA · PI ROY, SABITA · 2007 to 2011
$1.7M
Antiangiogenic Gene Therapy of Ovarian and Breast CancersR01CA114340 · NCI · UNIVERSITY OF MINNESOTA · PI RAMAKRISHNAN, SUNDARAM · 2007 to 2011
$1.3M
Role of Mu Opioid Receptor in Immune FunctionK02DA015349 · NIDA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI ROY, SABITA · 2002 to 2011
$977k
NCI NIH HHS CA114340NCI NIH HHS R01 CA114340NHLBI NIH HHS HL081715NHLBI NIH HHS R01 HL081715NHLBI NIH HHS T32 HL007741NHLBI NIH HHS T32HL007741NIDA NIH HHS DA011806NIDA NIH HHS DA022935NIDA NIH HHS K02 DA015349NIDA NIH HHS P50 DA011806NIDA NIH HHS R01 DA012104NIDA NIH HHS R01 DA022935
6 · The paper itself

Abstract

Adaptive changes to oxygen availability are critical for cell survival and tissue homeostasis. Prolonged oxygen deprivation due to reduced blood flow to cardiac or peripheral tissues can lead to myocardial infarction and peripheral vascular disease, respectively. Mammalian cells respond to hypoxia by modulating oxygen-sensing transducers that stabilize the transcription factor hypoxia-inducible factor 1α (HIF-1α), which transactivates genes governing angiogenesis and metabolic pathways. Oxygen-dependent changes in HIF-1α levels are regulated by proline hydroxylation and proteasomal degradation. Here we provide evidence for what we believe is a novel mechanism regulating HIF-1α levels in isolated human ECs during hypoxia. Hypoxia differentially increased microRNA-424 (miR-424) levels in ECs. miR-424 targeted cullin 2 (CUL2), a scaffolding protein critical to the assembly of the ubiquitin ligase system, thereby stabilizing HIF-α isoforms. Hypoxia-induced miR-424 was regulated by PU.1-dependent transactivation. PU.1 levels were increased in hypoxic endothelium by RUNX-1 and C/EBPα. Furthermore, miR-424 promoted angiogenesis in vitro and in mice, which was blocked by a specific morpholino. The rodent homolog of human miR-424, mu-miR-322, was significantly upregulated in parallel with HIF-1α in experimental models of ischemia. These results suggest that miR-322/424 plays an important physiological role in post-ischemic vascular remodeling and angiogenesis.

Indexed as

Neovascularization, PhysiologicAnimalsCell LineEndothelial CellsFemaleHumansHypoxiaHypoxia-Inducible Factor 1, alpha SubunitMaleMiceMice, NudeMicroarray AnalysisMicroRNAsOxygenProtein IsoformsRatsHypoxia-Inducible Factor 1, alpha SubunitMicroRNAsOxygenProtein Isoforms

Identifiers

PMID20972335
PMCPMC2964978
OpenAlexW2088161934

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.