Evidence map›Paper›PMID 42421074›Full record

ArticleCardiovascular diabetology2026

STIM1-dependent treg dysfunction promotes cardiometabolic HFpEF: insights from patients and animal studies.

Balaji Srinivas, Alluri Kiran, Hongmei Peng, Jiang Xu, Paula Fortuno, Jennifer May, Ismail El Moudden, Nour-Eddine Rhaleb, John M Herre, Raymond L Benza and 1 more

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Article in Cardiovascular diabetology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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.

Balaji SrinivasDepartment of Biomedical and Translational Sciences, Macon and Joan Brock Virginia Health Sciences at Old Dominion University, P.O. Box 1980, Norfolk, VA, 23501-1980, USA.
Alluri KiranDepartment of Biomedical and Translational Sciences, Macon and Joan Brock Virginia Health Sciences at Old Dominion University, P.O. Box 1980, Norfolk, VA, 23501-1980, USA.
Hongmei PengDepartment of Physiology, Wayne State University, Detroit, MI, 48202, USA.
Jiang XuDepartment of Physiology, Wayne State University, Detroit, MI, 48202, USA.
Paula FortunoDepartment of Biomedical and Translational Sciences, Macon and Joan Brock Virginia Health Sciences at Old Dominion University, P.O. Box 1980, Norfolk, VA, 23501-1980, USA.
Jennifer MaySentara Health Research Center, 800 Independence Blvd, Virginia Beach, Norfolk, VA, 23455, USA.
Ismail El MouddenVHS Healthcare Analytics Institute, Macon and Joan Brock Virginia Health Sciences at Old Dominion University, Norfolk, USA.
Nour-Eddine RhalebDepartment of Physiology, Wayne State University, Detroit, MI, 48202, USA.
John M HerreSentara Norfolk General Hospital, 600 Gresham Drive, Norfolk, VA, 23507, USA.
Raymond L BenzaMacon and Joan Brock Virginia Health Sciences at Old Dominion University, George and Linda Kaufman Academic Chair of Cardiology, Sentara Health. 825 Fairfax Ave, Suite 563, Norfolk, VA, 23507, USA.
Khalid MatrouguiDepartment of Biomedical and Translational Sciences, Macon and Joan Brock Virginia Health Sciences at Old Dominion University, P.O. Box 1980, Norfolk, VA, 23501-1980, USA. matrouk@odu.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHeart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown.

methodsCirculating Tregs from patients with and without HFpEF were analyzed for abundance, STIM1 expression, and stress-associated signaling pathways. To establish causality, mice with Treg-specific deletion of STIM1 (Treg

resultsPatients with HFpEF exhibited reduced circulating Treg numbers accompanied by increased STIM1 expression and activation of apoptotic, inflammatory, and ER stress pathways, consistent with stress-induced Treg instability. In vivo, control mice developed features of HFpEF, including diastolic dysfunction with preserved ejection fraction, hypertension, metabolic dysregulation, endothelial dysfunction, cardiac fibrosis, and impaired exercise tolerance. In contrast, Treg

conclusionsSTIM1-dependent stress signaling drives maladaptive Treg instability that amplifies cardiovascular inflammation and HFpEF progression. These findings identify Treg STIM1 as a key driver of immune-mediated HFpEF progression and provide mechanistic evidence from humans to mice supporting immune-targeted therapeutic strategies.

Indexed as

Heart FailureStroke VolumeStromal Interaction Molecule 1T-Lymphocytes, RegulatoryVentricular Function, LeftAgedAnimalsApoptosisCalcium SignalingCase-Control StudiesDisease Models, AnimalEndoplasmic Reticulum StressFemaleFibrosisHumansInflammation MediatorsInflammation MediatorsInterferon-gammaNeoplasm ProteinsSTIM1 protein, humanStim1 protein, mouseStromal Interaction Molecule 1ApoptosisCardiac fibrosisDiastolic dysfunctionER stressHFpEFInflammationSTIM1Treg cellsUnfolded protein responseVascular endothelial function

Identifiers

PMID42421074
PMCPMC13348757

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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.