Evidence mapPaperPMID 41002417Full record

ArticleCells2025

Empagliflozin Preserves Cardiomyocyte Structural Homeostasis via the Stabilization of the Integrin α5-Desmocollin-2 Adhesion Axis in Sepsis-Induced Cardiomyopathy.

Gan Qiao, Yongxiang Lu, Jianping Wu, Chunyang Ren, Minghua Liu, Sicheng Liang, Chunxiang Zhang

Abstract read
In one paragraph

Article in Cells, 2025. 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. 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

7 authors.

Gan QiaoDepartment of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Yongxiang LuDepartment of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Jianping WuDepartment of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Chunyang RenDepartment of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.ORCID 0009-0001-5708-0641
Minghua LiuDepartment of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Sicheng LiangDepartment of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
Chunxiang ZhangDepartment of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.ORCID 0000-0003-3308-0265

Funding

National Natural Science Foundation of China No# 82030007 and U23A20398
6 · The paper itself

Abstract

Sepsis-induced cardiomyopathy is a life-threatening complication lacking targeted therapies. While empagliflozin (Empa), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, confers robust cardioprotection, its specific efficacy in treating sepsis-induced cardiomyopathy and the Empa mechanisms remain poorly defined, limiting its targeted therapeutic use. In this study, we investigated Empa's effects and its novel mechanisms in a murine lipopolysaccharide (LPS)-induced model of septic cardiomyopathy. Empa pre-treatment effectively prevented LPS-induced cardiac dysfunction, preserving ejection fraction and mitigating myocardial injury (assessed by histology and ELISA) and fibrosis. Transcriptomic analysis revealed that Empa's protective effects were profoundly linked to the preservation of cardiomyocyte cytoskeletal pathways, alongside its anti-inflammatory actions. The results indicate that LPS induced a pathological dissociation of the matrix protein Integrin α5 (ITGA5) from the cell-cell adhesion protein Desmocollin-2 (DSC2), a structural disruption completely abrogated by Empa in vivo. This ITGA5-DSC2 stabilization was further confirmed to be a cardiomyocyte-intrinsic effect, recapitulated in vitro in both neonatal mouse cardiomyocytes and human AC16 cells. Building on this mechanistic insight, a computational design was successfully employed to develop 13 novel helical protein binders specifically targeting the ITGA5, yielding candidates with favorable structural properties as potential therapeutic leads. These findings establish the cardiomyocyte structural homeostasis via the ITGA5-DSC2 adhesion axis as a novel, key SGLT2-independent mechanism for empagliflozin's cardioprotection, revealing promising new therapeutic approaches for sepsis-induced cardiomyopathy.

Indexed as

Benzhydryl CompoundsCardiomyopathiesDesmocollinsGlucosidesHomeostasisMyocytes, CardiacSepsisAnimalsCell AdhesionDisease Models, AnimalHumansLipopolysaccharidesMaleMiceMice, Inbred C57BLSodium-Glucose Transporter 2 InhibitorsBenzhydryl CompoundsDesmocollinsempagliflozinGlucosidesLipopolysaccharidesSodium-Glucose Transporter 2 InhibitorscardiomyopathyDSC2empagliflozinITGA5sepsis

Identifiers

PMID41002417
PMCPMC12468141

What Socratic 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 Socratic graph.