Evidence map›Paper›PMID 36543116›Full record

ArticleCell reports. Medicine2022

MicroRNA-dependent suppression of biological pacemaker activity induced by TBX18.

Lizbeth Sanchez, Thassio Mesquita, Rui Zhang, Ke Liao, Russell Rogers, Yen-Nien Lin, Rodrigo Miguel-Dos-Santos, Akbarshakh Akhmerov, Liang Li, Asma Nawaz and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports. Medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

7 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025
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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

13 authors at 2 institutions in 1 country.

Lizbeth SanchezSmidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90048, USA.
Thassio MesquitaSmidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90048, USA.
Rui ZhangSmidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90048, USA.
Ke LiaoSmidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90048, USA.
Russell RogersSmidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90048, USA.
Yen-Nien LinSmidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90048, USA.
Rodrigo Miguel-Dos-SantosSmidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90048, USA.
Akbarshakh AkhmerovSmidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90048, USA.
Liang LiSmidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90048, USA.
Asma NawazSmidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90048, USA.
Kevin HolmSmidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90048, USA.
Eduardo MarbánSmidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90048, USA.
Eugenio CingolaniSmidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA 90048, USA. Electronic address: eugenio.cingolani@csmc.edu.
Cedars-Sinai Medical Center · USCedars-Sinai Smidt Heart Institute · US

Funding

Calcium Regulation in Heart Failure with Preserved versus Reduced Ejection FractionR01HL147570 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI CINGOLANI, EUGENIO, GOLDHABER, JOSHUA I · 2019 to 2022
$3.0M
American Heart Association-American Stroke Association 836665NHLBI NIH HHS R01 HL147570
6 · The paper itself

Abstract

Chemically modified mRNA (CMmRNA) with selectively altered nucleotides are used to deliver transgenes, but translation efficiency is variable. We have transfected CMmRNA encoding human T-box transcription factor 18 (CMmTBX18) into heart cells or the left ventricle of rats with atrioventricular block. TBX18 protein expression from CMmTBX18 is weak and transient, but Acriflavine, an Argonaute 2 inhibitor, boosts TBX18 levels. Small RNA sequencing identified two upregulated microRNAs (miRs) in CMmTBX18-transfected cells. Co-administration of miR-1-3p and miR-1b antagomiRs with CMmTBX18 prolongs TBX18 expression in vitro and in vivo and is sufficient to generate electrical stimuli capable of pacing the heart. Different suppressive miRs likewise limit the expression of VEGF-A CMmRNA. Cells therefore resist translation of CMmRNA therapeutic transgenes by upregulating suppressive miRs. Blockade of suppressive miRs enhances CMmRNA expression of genes driving biological pacing or angiogenesis. Such counterstrategies constitute an approach to boost the efficacy and efficiency of CMmRNA therapies.

Indexed as

MicroRNAsAnimalsBiological ClocksHumansMyocytes, CardiacRatsT-Box Domain ProteinsMicroRNAsT-Box Domain ProteinsTbx18 protein, humanTbx18 protein, ratAV blockBiological pacemakercell reprogrammingchemically modified mRNAiSAN cellsmicroRNAsRNA therapiessmall RNAsTbx18transcription factors

Identifiers

PMID36543116
PMCPMC9798022
OpenAlexW4312082732

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.