Evidence map›Paper›PMID 41766527›Full record

ArticleCirculation2026

Small Extracellular Vesicle External Surface Adiponectin-Mediated Adipocytes/Cardiomyocytes Communication in Diabetic Ischemic Heart Failure.

Zhen Zhang, Di Zhu, Caihong Liu, Lu Gan, Jianli Zhao, Zhijun Meng, Peng Yao, Demin Liu, Guoqiang Gu, Bernard Lopez and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

13 authors.

Zhen ZhangDepartment of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (Z.Z., D.Z., C.L., L.G., Z.M., P.Y., D.L., G.G., B.L., T.C., X.M.).
Di ZhuDepartment of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (Z.Z., D.Z., C.L., L.G., Z.M., P.Y., D.L., G.G., B.L., T.C., X.M.).
Caihong LiuDepartment of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (Z.Z., D.Z., C.L., L.G., Z.M., P.Y., D.L., G.G., B.L., T.C., X.M.).
Lu GanDepartment of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (Z.Z., D.Z., C.L., L.G., Z.M., P.Y., D.L., G.G., B.L., T.C., X.M.).ORCID 0000-0001-8665-2760
Jianli ZhaoDepartment of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL (J.Z., Y.W.).ORCID 0000-0003-4662-2940
Zhijun MengDepartment of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (Z.Z., D.Z., C.L., L.G., Z.M., P.Y., D.L., G.G., B.L., T.C., X.M.).ORCID 0000-0002-2152-6664
Peng YaoDepartment of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (Z.Z., D.Z., C.L., L.G., Z.M., P.Y., D.L., G.G., B.L., T.C., X.M.).ORCID 0000-0002-6996-6167
Demin LiuDepartment of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (Z.Z., D.Z., C.L., L.G., Z.M., P.Y., D.L., G.G., B.L., T.C., X.M.).ORCID 0000-0002-8784-1026
Guoqiang GuDepartment of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (Z.Z., D.Z., C.L., L.G., Z.M., P.Y., D.L., G.G., B.L., T.C., X.M.).
Bernard LopezDepartment of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (Z.Z., D.Z., C.L., L.G., Z.M., P.Y., D.L., G.G., B.L., T.C., X.M.).ORCID 0000-0001-6309-4575
Theodore A ChristopherDepartment of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (Z.Z., D.Z., C.L., L.G., Z.M., P.Y., D.L., G.G., B.L., T.C., X.M.).
Yajing WangDepartment of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL (J.Z., Y.W.).ORCID 0000-0002-6358-6948
Xinliang MaDepartment of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (Z.Z., D.Z., C.L., L.G., Z.M., P.Y., D.L., G.G., B.L., T.C., X.M.).ORCID 0000-0002-9041-0876

Funding

Project 3 - Role of Proline Metabolism in Regulation of Mammalian Cardiomyocyte ProliferationP01HL160476 · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2025 to 2025
$2.1M
Targeting Adiponectin for Cardioprotection in the Ischemic HeartR01HL096686 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI XIN-LIANG MA, Yajing Wang · 2022 to 2024
$1.2M
Cav-3 in Diabetic Myocardial Injury Following Ischemia/ReperfusionR01HL123404 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI XIN-LIANG MA · 2021 to 2023
$1.2M
Improving Cardiac Microenvironment as a Novel Strategy against Diabetic Ischemic Heart FailureR01HL173090 · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2025 to 2025
$638k
NHLBI NIH HHS P01 HL160476NHLBI NIH HHS R01 HL096686NHLBI NIH HHS R01 HL123404NHLBI NIH HHS R01 HL173090
6 · The paper itself

Abstract

backgroundMortality from acute myocardial infarction (MI) has declined significantly in the past decade for nondiabetic patients. However, both morbidity and mobility of ischemic heart failure (IHF) persistently escalate in the diabetic population via incompletely understood mechanisms. Recent studies demonstrated that small extracellular vesicles (sEVs) released from nondiabetic and diabetic adipocytes (ADps) exert opposite effects on acute myocardial ischemia and reperfusion (MI/R) injury. However, whether and how ADp sEVs may protect against post-MI remodeling and IHF, and more important, whether and how diabetes may impair this protective effect, remain unknown.

methodssEVs were isolated from epididymal fat pads of nondiabetic animals and intramyocardially injected in nondiabetic or diabetic hearts subjected to MI (90 minutes of MI per 4 weeks of reperfusion).

resultssEV treatment significantly attenuated post-MI cardiac remodeling and improved cardiac function in nondiabetic mice. However, the protection was not observed in diabetic hearts. In adult cardiomyocytes isolated from nondiabetic hearts, sEVs rapidly (15 minutes) activated cell salvage kinases (ERK [extracellular signal-regulated kinase], AMPK [AMP-activated protein kinase], and ACC [acetyl-CoA carboxylase]) and suppressed oxidative stress-induced cell death, suggesting sEV external surface molecules are responsible for the observed cytoprotection. The Exo-Flow (a technology detecting sEV external surface molecules) demonstrated that adiponectin (APN) is enriched on the sEV external surface. The sEVs from APN knockout mice or APN neutralization (NU) antibody pretreated sEVs failed to protect the heart against IHF. Moreover, the cardioprotective effects of sEVs were abolished in APN receptor-1 (AdipoR1)-deficient mice (the primary receptor for APN signaling in the heart) or in mice overexpressing GRK2 (G-protein-coupled receptor kinase 2, a kinase that phosphorylates and inactivates AdipoR1). Finally, diabetes significantly increased cardiac GRK2 expression and AdipoR1 phosphorylation, which prevented sEVs from exerting their beneficial effects. Restoring AdipoR1 function by knockin a mutated phosphorylation-resistant AdipoR1 (AdipoR1

conclusionsOur study reveals that APN is enriched on the ADp-derived external surface of sEVs and is biologically active, playing a critical role in ADp-cardiomyocyte communication. Diabetes disrupts this communication by enhancing GRK2-mediated AdipoR1 phosphorylation, impairing sEV signaling, and exacerbating IHF. These findings provide new insights into the pathophysiology and therapy of IHF in diabetes.

Indexed as

adipocyteadiponectindiabetesischemic heart failuresmall extracellular vesicle

Identifiers

PMID41766527
PMCPMC12965755

What Socratic holds

Textmetadata
LicenceTDM
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.