Evidence map›Paper›PMID 23233752›Full record

Trial reportCirculation research2013

MicroRNA-15a and microRNA-16 impair human circulating proangiogenic cell functions and are increased in the proangiogenic cells and serum of patients with critical limb ischemia.

Gaia Spinetti, Orazio Fortunato, Andrea Caporali, Saran Shantikumar, Micol Marchetti, Marco Meloni, Betty Descamps, Ilaria Floris, Elena Sangalli, Rosa Vono and 5 more

Open access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed, 2 pooled it
7.5field-weighted citation impact, top 2% 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

108 citing papers in PubMed, 2 syntheses or guidelines pooled it, 200 citations in OpenAlex.

  1. Pooled it
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  6. Review
  7. miRNA-6236 Regulation of Postischemic Skeletal Muscle Angiogenesis.Journal of the American Heart Association · 2024
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48 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

15 authors at 3 institutions in 1 country.

Gaia SpinettiMultiMedica, Milan, Italy.
Orazio Fortunato
Andrea Caporali
Saran Shantikumar
Micol Marchetti
Marco Meloni
Betty Descamps
Ilaria Floris
Elena Sangalli
Rosa Vono
Ezio Faglia
Claudia Specchia
Gianfranco Pintus
Paolo Madeddu
Costanza Emanueli
MultiMedica · ITUniversity of Brescia · ITIstituti di Ricovero e Cura a Carattere Scientifico · IT

Funding

British Heart Foundation FS/05/113/19965British Heart Foundation FS/10/61/28566British Heart Foundation FS/11/52/29018British Heart Foundation PG/10/81/28606
6 · The paper itself

Abstract

rationaleCirculating proangiogenic cells (PACs) support postischemic neovascularization. Cardiovascular disease and diabetes mellitus impair PAC regenerative capacities via molecular mechanisms that are not fully known. We hypothesize a role for microRNAs (miRs). Circulating miRs are currently investigated as potential diagnostic and prognostic biomarkers.

objectiveThe objectives were the following: (1) to profile miR expression in PACs from critical limb ischemia (CLI) patients; (2) to demonstrate that miR-15a and miR-16 regulate PAC functions; and (3) to characterize circulating miR-15a and miR-16 and to investigate their potential biomarker value. METHODS AND

resultsTwenty-eight miRs potentially able to modulate angiogenesis were measured in PACs from CLI patients with and without diabetes mellitus and controls. miR-15a and miR-16 were further analyzed. CLI-PACs expressed higher level of mature miR-15a and miR-16 and of the primary transcript pri-miR-15a/16-1. miR-15a/16 overexpression impaired healthy PAC survival and migration. Conversely, miR-15a/16 inhibition improved CLI-PAC-defective migration. Vascular endothelial growth factor-A and AKT-3 were validated as direct targets of the 2 miRs, and their protein levels were reduced in miR-15a/16-overexpressing healthy PACs and in CLI-PACs. Transplantation of healthy PACs ex vivo-engineered with anti-miR-15a/16 improved postischemic blood flow recovery and muscular arteriole density in immunodeficient mice. miR-15a and miR-16 were present in human blood, including conjugated to argonaute-2 and in exosomes. Both miRs were increased in the serum of CLI patients and positively correlated with amputation after restenosis at 12 months postrevascularization of CLI type 2 diabetes mellitus patients. Serum miR-15a additionally correlated with restenosis at follow-up.

conclusionsEx vivo miR-15a/16 inhibition enhances PAC therapeutic potential, and circulating miR-15a and miR-16 deserves further investigation as a prognostic biomarker in CLI patients undergoing revascularization.

Indexed as

AnimalsCell MovementCells, CulturedCell SurvivalCell TransplantationDiabetes ComplicationsDiabetes Mellitus, Type 2HEK293 CellsHindlimbHumansIschemiaMiceMice, NudeMicroRNAsNeovascularization, PathologicMicroRNAsMIRN15 microRNA, humanMIRN16 microRNA, human

Identifiers

PMID23233752
PMCPMC3616367
OpenAlexW2086692553

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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.