Evidence map›Paper›PMID 39896622›Full record

ArticlebioRxiv : the preprint server for biology2025

Glycoprotein 130 Antagonism Counteracts Metabolic and Inflammatory Alterations to Enhance Right Ventricle Function in Pulmonary Artery Banded Pigs.

Jenna B Mendelson, Jacob D Sternbach, Ryan A Moon, Lynn M Hartweck, Sophia R Clark, Walt Tollison, Matthew T Lahti, John P Carney, Todd Markowski, LeeAnn Higgins and 2 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Jenna B MendelsonDepartment of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN.ORCID 0000-0002-8229-385X
Jacob D SternbachLillehei Heart Institute, Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN.
Ryan A MoonLillehei Heart Institute, Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN.
Lynn M HartweckLillehei Heart Institute, Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN.
Sophia R ClarkLillehei Heart Institute, Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN.
Walt TollisonExperimental Surgical Services Laboratory, Department of Surgery, University of Minnesota, Minneapolis, MN.
Matthew T LahtiExperimental Surgical Services Laboratory, Department of Surgery, University of Minnesota, Minneapolis, MN.
John P CarneyExperimental Surgical Services Laboratory, Department of Surgery, University of Minnesota, Minneapolis, MN.
Todd MarkowskiCenter for Metabolomics and Proteomics, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN.
LeeAnn HigginsCenter for Metabolomics and Proteomics, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN.
Felipe KazmirczakLillehei Heart Institute, Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN.
Kurt W PrinsLillehei Heart Institute, Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN.ORCID 0000-0002-0364-6742

Funding

TRAINING PROGRAM IN MUSCLE RESEARCHT32AR007612 · NIAMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI JAMES M ERVASTI, DAWN A LOWE · 2001 to 2026
$11.3M
GP130 Antagonism in Porcine RV Pressure OverloadR01HL162927 · NHLBI · UNIVERSITY OF MINNESOTA · PI Kurt W Prins · 2022 to 2026
$3.3M
Multi-scale Investigation of Sex Differences in Right Ventricular Function via Estrogen-Microtubule InteractionsR01HL158795 · NHLBI · UNIVERSITY OF MINNESOTA · PI Kurt W Prins · 2022 to 2026
$2.8M
A transformative next-generation Orbitrap Tribrid system for the UMN and Upper MidwestS10OD028717 · OD · UNIVERSITY OF MINNESOTA · PI GRIFFIN, TIMOTHY J. · 2020 to 2020
$1.2M
Modulating the Microbiome to Enhance Right Ventricular Function in Pulmonary Arterial HypertensionK08HL168166 · NHLBI · UNIVERSITY OF MINNESOTA · PI Sasha Zheng Prisco · 2024 to 2026
$525k
Mechanisms of Large Animal RV DysfunctionF31HL170585 · NHLBI · UNIVERSITY OF MINNESOTA · PI MENDELSON, JENNA BLAIR · 2024 to 2025
$71k
NHLBI NIH HHS F31 HL170585NHLBI NIH HHS K08 HL168166NHLBI NIH HHS R01 HL158795NHLBI NIH HHS R01 HL162927NIAMS NIH HHS T32 AR007612NIH HHS S10 OD028717
6 · The paper itself

Abstract

Background: Right ventricular dysfunction (RVD) is a risk factor for death in multiple cardiovascular diseases, but RV-enhancing therapies are lacking. Inhibition of glycoprotein-130 (GP130) signaling with the small molecule SC144 improves RV function in rodent RVD via anti-inflammatory and metabolic mechanisms. However, SC144's efficacy and molecular effects in a translational large animal model of RVD are unknown. Methods: 4-week-old castrated male pigs underwent pulmonary artery banding (PAB). After 3 weeks, PAB pigs were randomized into 2 groups (daily injections of SC144 [2.2 mg/kg, PAB-SC144, Results: SC144 significantly improved RV ejection fraction (Control: 60±4%, PAB-Veh: 22±10%, PAB-SC144: 37±6%) despite similar RV afterload. Single-nucleus RNA sequencing demonstrated PAB-Veh pigs had lower cardiomyocyte and higher macrophage/lymphocyte/pericyte/endothelial cell abundances as compared to control, and many of these changes were blunted by SC144. SC144 combatted the downregulation of cardiomyocyte metabolic genes induced by PAB. Kinome enrichment analysis suggested SC144 counteracted RV mTORC1 activation. Correspondingly, SC144 rebalanced RV autophagy pathway proteins and improved mitochondrial morphology. Integrated lipidomics, metabolomics, and proteomics analyses revealed SC144 restored fatty acid metabolism. Finally, CellChat analysis revealed SC144 restored pericyte-endothelial cell cross-talk. Conclusion: GP130 antagonism blunts elevated immune cell abundance, reduces pro-inflammatory gene transcription in macrophages and lymphocytes, rebalances autophagy and preserves fatty acid metabolism in cardiomyocytes, and restores endothelial cell and pericyte communication to improve RV function.

Identifiers

PMID39896622
PMCPMC11785131

What Socratic holds

Textmetadata
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.