Evidence map›Paper›PMID 37707956›Full record

ArticleJCI insight2023

Circulating extracellular vesicles in human cardiorenal syndrome promote renal injury in a kidney-on-chip system.

Emeli Chatterjee, Rodosthenis S Rodosthenous, Ville Kujala, Priyanka Gokulnath, Michail Spanos, Helge Immo Lehmann, Getulio Pereira de Oliveira, Mingjian Shi, Tyne W Miller-Fleming, Guoping Li and 9 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03345446 (Circulating RNAs in Acute Heart Failure), which is not on this map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.6field-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.

NCT03345446 active not recruitingnot on this map

Circulating RNAs in Acute Heart Failure

TypeobservationalSponsorMassachusetts General HospitalRan2016 to 2026Enrolled200ConditionsAcute Congestive Heart Failure, Heart Failure With Reduced Ejection Fraction, Heart Failure With Normal Ejection FractionArmsCardiac MRI
3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 30 citations in OpenAlex.

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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

19 authors at 7 institutions in 2 countries.

Emeli ChatterjeeCardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Rodosthenis S RodosthenousCardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Ville KujalaEmulate, Inc., Boston, Massachusetts, USA.
Priyanka GokulnathCardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Michail SpanosCardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Helge Immo LehmannCardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Getulio Pereira de OliveiraDepartment of Anesthesia, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Mingjian ShiDepartment of Biomedical Informatics and.
Tyne W Miller-FlemingDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Guoping LiCardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Ionita Calin GhiranDepartment of Anesthesia, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Katia KaralisEmulate, Inc., Boston, Massachusetts, USA.
JoAnn LindenfeldDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Jonathan D MosleyDepartment of Biomedical Informatics and.
Emily S LauCardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Jennifer E HoCardiovascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Quanhu ShengDepartment of Biostatistics and.
Ravi ShahVanderbilt Translational and Clinical Research Center, Cardiology Division, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Saumya DasCardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Massachusetts General Hospital · USVanderbilt University Medical Center · USBeth Israel Deaconess Medical Center · USBoston University · USEmulate (United States) · USRegeneron (United States) · USUniversity of Helsinki · FI

Funding

Functional role and therapeutic targeting of exosomes and extracellular RNA biomarkers in heart failureR35HL150807 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Saumya Das · 2020 to 2026
$6.7M
Molecular dissection and imaging of extracellular vesicles to define their origin and targetsUH3TR002878 · NCATS · MASSACHUSETTS GENERAL HOSPITAL · PI DAS, SAUMYA, TALISMAN, TIJANA · 2021 to 2022
$2.2M
HFpEF Susceptibility in Women: The Role of InflammationK23HL159243 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Emily Lau · 2022 to 2026
$1.1M
NCATS NIH HHS UH3 TR002878NHLBI NIH HHS K23 HL159243NHLBI NIH HHS R35 HL150807
6 · The paper itself

Abstract

BACKGROUNDCardiorenal syndrome (CRS) - renal injury during heart failure (HF) - is linked to high morbidity. Whether circulating extracellular vesicles (EVs) and their RNA cargo directly impact its pathogenesis remains unclear.METHODSWe investigated the role of circulating EVs from patients with CRS on renal epithelial/endothelial cells using a microfluidic kidney-on-chip (KOC) model. The small RNA cargo of circulating EVs was regressed against serum creatinine to prioritize subsets of functionally relevant EV-miRNAs and their mRNA targets investigated using in silico pathway analysis, human genetics, and interrogation of expression in the KOC model and in renal tissue. The functional effects of EV-RNAs on kidney epithelial cells were experimentally validated.RESULTSRenal epithelial and endothelial cells in the KOC model exhibited uptake of EVs from patients with HF. HF-CRS EVs led to higher expression of renal injury markers (IL18, LCN2, HAVCR1) relative to non-CRS EVs. A total of 15 EV-miRNAs were associated with creatinine, targeting 1,143 gene targets specifying pathways relevant to renal injury, including TGF-β and AMPK signaling. We observed directionally consistent changes in the expression of TGF-β pathway members (BMP6, FST, TIMP3) in the KOC model exposed to CRS EVs, which were validated in epithelial cells treated with corresponding inhibitors and mimics of miRNAs. A similar trend was observed in renal tissue with kidney injury. Mendelian randomization suggested a role for FST in renal function.CONCLUSIONPlasma EVs in patients with CRS elicit adverse transcriptional and phenotypic responses in a KOC model by regulating biologically relevant pathways, suggesting a role for EVs in CRS.TRIAL REGISTRATIONClinicalTrials.gov NCT03345446.FUNDINGAmerican Heart Association (AHA) (SFRN16SFRN31280008); National Heart, Lung, and Blood Institute (1R35HL150807-01); National Center for Advancing Translational Sciences (UH3 TR002878); and AHA (23CDA1045944).

Indexed as

Cardio-Renal SyndromeExtracellular VesiclesHeart FailureMicroRNAsEndothelial CellsHumansKidneyTransforming Growth Factor betaMicroRNAsTransforming Growth Factor betaCardiologyFibrosisHeart failureNephrologyNoncoding RNAs

Identifiers

PMID37707956
PMCPMC10721327
OpenAlexW4386741909

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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 OpenQuestion graph.