Evidence mapPaperPMID 35911183Full record

ArticlePulmonary circulation2022

l-Carnitine therapy improves right heart dysfunction through Cpt1-dependent fatty acid oxidation.

Vineet Agrawal, Anna R Hemnes, Nicholas J Shelburne, Niki Fortune, Julio L Fuentes, Dan Colvin, Marion W Calcutt, Megha Talati, Emily Poovey, James D West and 1 more

Open access · goldAbstract read
In one paragraph

Article in Pulmonary circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
4.3field-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.

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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
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  6. Observational
  7. Article
  8. Article
  9. Review
  10. Review
  11. The therapeutic landscape of citrin deficiency.Journal of inherited metabolic disease · 2024
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Mitochondrial Integrity Is Critical in Right Heart Failure Development.International journal of molecular sciences · 2023
    Review
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  18. Article
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

11 authors at 2 institutions in 1 country.

Vineet AgrawalDepartment of Medicine, Division of Cardiovascular Medicine Vanderbilt University Medical Center Nashville Tennessee USA.ORCID 0000-0002-8457-6722
Anna R HemnesDepartment of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine Vanderbilt University Medical Center Nashville Tennessee USA.
Nicholas J ShelburneDepartment of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine Vanderbilt University Medical Center Nashville Tennessee USA.ORCID 0000-0003-3008-9555
Niki FortuneDepartment of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine Vanderbilt University Medical Center Nashville Tennessee USA.
Julio L FuentesDepartment of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine Vanderbilt University Medical Center Nashville Tennessee USA.
Dan ColvinVanderbilt University Institute of Imaging Vanderbilt University Nashville Tennessee USA.
Marion W CalcuttDepartment of Biochemistry Vanderbilt University Nashville Tennessee USA.
Megha TalatiDepartment of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine Vanderbilt University Medical Center Nashville Tennessee USA.
Emily PooveyDepartment of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine Vanderbilt University Medical Center Nashville Tennessee USA.
James D WestDepartment of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine Vanderbilt University Medical Center Nashville Tennessee USA.
Evan L BrittainDepartment of Medicine, Division of Cardiovascular Medicine Vanderbilt University Medical Center Nashville Tennessee USA.
Vanderbilt University Medical Center · USVanderbilt University · US

Funding

Interdisciplinary Training Program in Lung ResearchT32HL094296 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · 2023 to 2025
$836k
Network Medicine and Systems Pharmacology to Advance Precision Medicine in Combined Pulmonary HypertensionR01HL163960 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2025 to 2025
$700k
Mentorship in Pulmonary Vascular DiseaseK24HL155891 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · 2023 to 2025
$344k
NHLBI NIH HHS K08 HL153956NHLBI NIH HHS K24 HL155891NHLBI NIH HHS R01 HL095797NHLBI NIH HHS R01 HL122417NHLBI NIH HHS R01 HL163960NHLBI NIH HHS T32 HL094296
6 · The paper itself

Abstract

Pulmonary arterial hypertension (PAH) is a fatal vasculopathy that ultimately leads to elevated pulmonary pressure and death by right ventricular (RV) failure, which occurs in part due to decreased fatty acid oxidation and cytotoxic lipid accumulation. In this study, we tested the hypothesis that decreased fatty acid oxidation and increased lipid accumulation in the failing RV is driven, in part, by a relative carnitine deficiency. We then tested whether supplementation of l-carnitine can reverse lipotoxic RV failure through augmentation of fatty acid oxidation. In vivo in transgenic mice harboring a human BMPR2 mutation, l-carnitine supplementation reversed RV failure by increasing RV cardiac output, improving RV ejection fraction, and decreasing RV lipid accumulation through increased PPARγ expression and augmented fatty acid oxidation of long chain fatty acids. These findings were confirmed in a second model of pulmonary artery banding-induced RV dysfunction. In vitro, l-carnitine supplementation selectively increased fatty acid oxidation in mitochondria and decreased lipid accumulation through a Cpt1-dependent pathway. l-Carnitine supplementation improves right ventricular contractility in the stressed RV through augmentation of fatty acid oxidation and decreases lipid accumulation. Correction of carnitine deficiency through l-carnitine supplementation in PAH may reverse RV failure.

Indexed as

metabolismpulmonary arterial hypertensionright heart failure

Identifiers

PMID35911183
PMCPMC9326551
OpenAlexW4285006793

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.