Evidence map›Paper›PMID 37408206›Full record

ArticleCells2023

Cardiovascular Protective Effects of NP-6A4, a Drug with the FDA Designation for Pediatric Cardiomyopathy, in Female Rats with Obesity and Pre-Diabetes.

Anthony M Belenchia, Asma Boukhalfa, Vincent G DeMarco, Alexander Mehm, Abuzar Mahmood, Pei Liu, Yinian Tang, Madhavi P Gavini, Brian Mooney, Howard H Chen and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2023. 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
2.5field-weighted citation impact, top 11% 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, 8 citations in OpenAlex.

  1. Article
  2. The angiotensin II type 2 receptor attenuates aging-associated arterial stiffness in female mice.American journal of physiology. Heart and circulatory physiology · 2025
    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

11 authors at 4 institutions in 1 country.

Anthony M BelenchiaDalton Cardiovascular Research Center and Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA.
Asma BoukhalfaMolecular Cardiology Research Institute, Tufts Medical Center, and Department of Medicine, Tufts University, Boston, MA 02111, USA.
Vincent G DeMarcoDepartment of Medicine, University of Missouri, Columbia, MO 65212, USA.
Alexander MehmMolecular Cardiology Research Institute, Tufts Medical Center, and Department of Medicine, Tufts University, Boston, MA 02111, USA.
Abuzar MahmoodDepartment of Neuroscience, Brandeis University, Waltham, MA 02453, USA.
Pei LiuCharles W. Gehrke Proteomics Center, University of Missouri, Columbia, MO 65211, USA.
Yinian TangMolecular Cardiology Research Institute, Tufts Medical Center, and Department of Medicine, Tufts University, Boston, MA 02111, USA.
Madhavi P GaviniNovopyxis Inc., Boston, MA 02108, USA.
Brian MooneyCharles W. Gehrke Proteomics Center, University of Missouri, Columbia, MO 65211, USA.
Howard H ChenMolecular Cardiology Research Institute, Tufts Medical Center, and Department of Medicine, Tufts University, Boston, MA 02111, USA.
Lakshmi PulakatDalton Cardiovascular Research Center and Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA.
University of Missouri · USTufts Medical Center · USBrandeis University · USTufts University · US

Funding

Mechanisms for Sex Differences in CVD Pathology and Development of a Targeted TherapeuticR01HL138988 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI JAFFE, IRIS Z, PULAKAT, LAKSHMIDEVI · 2018 to 2021
$2.6M
Multiplexed Molecular Imaging of Cell Death PathwaysR00HL121152 · NHLBI · TUFTS MEDICAL CENTER · PI CHEN, HOWARD H. · 2017 to 2019
$747k
Multiplexed Molecular Imaging of Cell Death PathwaysK99HL121152 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI CHEN, HOWARD H. · 2014 to 2015
$298k
NHLBI NIH HHS K99 HL121152NHLBI NIH HHS R00 HL121152NHLBI NIH HHS R01 HL138988NIH HHS R01HL138988-01A1 (LP)
6 · The paper itself

Abstract

backgroundObese and pre-diabetic women have a higher risk for cardiovascular death than age-matched men with the same symptoms, and there are no effective treatments. We reported that obese and pre-diabetic female Zucker Diabetic Fatty (ZDF-F) rats recapitulate metabolic and cardiac pathology of young obese and pre-diabetic women and exhibit suppression of cardio-reparative AT2R. Here, we investigated whether NP-6A4, a new AT2R agonist with the FDA designation for pediatric cardiomyopathy, mitigate heart disease in ZDF-F rats by restoring AT2R expression.

methodsZDF-F rats on a high-fat diet (to induce hyperglycemia) were treated with saline, NP-6A4 (10 mg/kg/day), or NP-6A4 + PD123319 (AT2R-specific antagonist, 5 mg/kg/day) for 4 weeks (n = 21). Cardiac functions, structure, and signaling were assessed by echocardiography, histology, immunohistochemistry, immunoblotting, and cardiac proteome analysis.

resultsNP-6A4 treatment attenuated cardiac dysfunction, microvascular damage (-625%) and cardiomyocyte hypertrophy (-263%), and increased capillary density (200%) and AT2R expression (240%) (

conclusionsCardiac autophagy impairment underlies heart disease induced by obesity and pre-diabetes, and there are no drugs to re-activate autophagy. We propose that NP-6A4 can be an effective drug to reactivate cardiac autophagy and treat obesity- and pre-diabetes-induced heart disease, particularly for young and obese women.

Indexed as

CardiomyopathiesHeart DiseasesHyperglycemiaPrediabetic StateAnimalsFemaleObesityRatsRats, ZuckerAngiotensin II receptor AT2 (AT2R)body mass index (BMI)cardiovascular disease (CVD)obesityZucker diabetic fatty-female (ZDF-F)Zucker diabetic fatty-male (ZDF-M)Zucker lean-female (ZL-F)Zucker lean-male (ZL-M)

Identifiers

PMID37408206
PMCPMC10216951
OpenAlexW4376274846

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.