Evidence map›Paper›PMID 38175760›Full record

ArticleCardiovascular research2024

Gene therapy encoding cell cycle factors to treat chronic ischemic heart failure in rats.

Riham R E Abouleisa, Xian-Liang Tang, Qinghui Ou, Abou-Bakr M Salama, Amie Woolard, Dana Hammouri, Hania Abdelhafez, Sarah Cayton, Sameeha K Abdulwali, Momo Arai and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.2field-weighted citation impact, top 24% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
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

14 authors at 2 institutions in 4 countries.

Riham R E AbouleisaDepartment of Medicine, Institute of Molecular Cardiology, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
Xian-Liang TangDepartment of Medicine, Institute of Molecular Cardiology, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
Qinghui OuDepartment of Medicine, Institute of Molecular Cardiology, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
Abou-Bakr M SalamaDepartment of Medicine, Institute of Molecular Cardiology, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
Amie WoolardDepartment of Medicine, Institute of Molecular Cardiology, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
Dana HammouriDepartment of Medicine, Institute of Molecular Cardiology, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
Hania AbdelhafezDepartment of Medicine, Institute of Molecular Cardiology, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
Sarah CaytonDepartment of Medicine, Institute of Molecular Cardiology, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
Sameeha K AbdulwaliDepartment of Medicine, Institute of Molecular Cardiology, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
Momo AraiDepartment of Medicine, Institute of Molecular Cardiology, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
Israel D SithuDepartment of Medicine, Center for Cardiometabolic Science, Envirome Institute, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
Daniel J ConklinDepartment of Medicine, Center for Cardiometabolic Science, Envirome Institute, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
Roberto BolliDepartment of Medicine, Institute of Molecular Cardiology, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.ORCID 0000-0002-9160-8614
Tamer M A MohamedDepartment of Medicine, Institute of Molecular Cardiology, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.ORCID 0009-0003-4462-7307
University of Louisville · USAlfaisal University · SA

Funding

Tumor Necrosis Factor Modulation of CPCsP01HL078825 · NHLBI · UNIVERSITY OF LOUISVILLE · PI BOLLI, ROBERTO · 2005 to 2021
$37.6M
TBDP30GM127607 · NIGMS · UNIVERSITY OF LOUISVILLE · PI HILL, BRADFORD GUY · 2018 to 2022
$6.3M
Induction of Cardiomyocyte Proliferation via Transient Expression of Cell Cycle Factors as a Promising Therapy for Heart FailureR01HL147921 · NHLBI · UNIVERSITY OF LOUISVILLE · PI Tamer M A Mohamed, Jonathan Satin · 2020 to 2026
$5.3M
Mechanisms of L-type Calcium Channel Regulation in Heart Health and DiseaseR01HL166280 · NHLBI · UNIVERSITY OF KENTUCKY · PI Jonathan Satin · 2023 to 2026
$2.5M
Defining the major signaling mechanism which controls spontaneous cardiomyocyte proliferation in the Neonatal StageR01HL178610 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI Tamer M A Mohamed · 2025 to 2026
$1.5M
Triple Gene Therapy for Ischemic Heart FailureR61HL177472 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI MOHAMED, TAMER M A, ROSENGART, TODD K · 2025 to 2025
$560k
Physiologically relevant cardiac tissue culture model for drug testing and disease modelingR15HL168688 · NHLBI · UNIVERSITY OF LOUISVILLE · PI GIRIDHARAN, GURUPRASAD A · 2023 to 2023
$464k
Deciphering the Relationship Between Cardiomyocyte Metabolic Configuration and Cell Cycle Re-entryF32HL149140 · NHLBI · UNIVERSITY OF LOUISVILLE · PI ABOULEISA, RIHAM RAAFAT ELGHARIB · 2020 to 2023
$243k
NHLBI NIH HHS F32 HL149140NHLBI NIH HHS P01 HL078825NHLBI NIH HHS R01 HL147921NHLBI NIH HHS R01 HL166280NHLBI NIH HHS R01 HL178610NHLBI NIH HHS R15 HL168688NHLBI NIH HHS R61 HL177472NIGMS NIH HHS P30 GM127607NIH HHS F32HL149140
6 · The paper itself

Abstract

aimsGene therapies to induce cardiomyocyte (CM) cell cycle re-entry have shown a potential to treat subacute ischaemic heart failure (IHF) but have not been tested in the more relevant setting of chronic IHF. Our group recently showed that polycistronic non-integrating lentivirus encoding Cdk1/CyclinB1 and Cdk4/CyclinD1 (TNNT2-4Fpolycistronic-NIL) is effective in inducing CM cell cycle re-entry and ameliorating subacute IHF models and preventing the subsequent IHF-induced congestions in the liver, kidneys, and lungs in rats and pigs. Here, we aim to test the long-term efficacy of TNNT2-4Fpolycistronic-NIL in a rat model of chronic IHF, a setting that differs pathophysiologically from subacute IHF and has greater clinical relevance. METHODS AND

resultsRats were subjected to a 2-h coronary occlusion followed by reperfusion; 4 weeks later, rats were injected intramyocardially with either TNNT2-4Fpolycistronic-NIL or LacZ-NIL. Four months post-viral injection, TNNT2-4Fpolycistronic-NIL-treated rats showed a significant reduction in scar size and a significant improvement in left ventricular (LV) systolic cardiac function but not in the LV dilatation associated with chronic IHF. A mitosis reporter system developed in our lab showed significant induction of CM mitotic activity in TNNT2-4Fpolycistronic-NIL-treated rats.

conclusionThis study demonstrates, for the first time, that TNNT2-4Fpolycistronic-NIL gene therapy induces CM cell cycle re-entry in chronic IHF and improves LV function, and that this salubrious effect is sustained for at least 4 months. Given the high prevalence of chronic IHF, these results have significant clinical implications for developing a novel treatment for this deadly disease.

Indexed as

Heart FailureMyocardial IschemiaAnimalsCell CycleChronic DiseaseGenetic TherapyMyocytes, CardiacRatsSwineCardiomyocyteCell cycleHeart failure

Identifiers

PMID38175760
PMCPMC10936750
OpenAlexW4390631689

What OpenQuestion holds

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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.