Evidence mapPaperPMID 41535924Full record

ArticleCardiovascular diabetology2026

Sympathetic-like-integrated engineered heart tissue models AGEs-induced adverse remodeling.

Yu-Hong Wang, Xi-Ming Zhu, Xiang Long, Shuo-Ji Zhu, Ting-Ting Liu, Moussa Ide Nasser, Zi-Ming Liao, Jia-Cheng Shi, Shu-Ting Zhang, Jia-Lin Liao and 4 more

Abstract read
In one paragraph

Article in Cardiovascular diabetology, 2026. 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

14 authors.

Yu-Hong WangAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China.
Xi-Ming ZhuAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China.
Xiang LongDepartment of Endocrinology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510100, China.
Shuo-Ji ZhuDepartment of Endocrinology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510100, China.
Ting-Ting LiuDepartment of Laboratory Diagnosis, The 971th Hospital, Qingdao, 266000, China.
Moussa Ide NasserDepartment of Endocrinology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510100, China.
Zi-Ming LiaoAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China.
Jia-Cheng ShiAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China.
Shu-Ting ZhangDepartment of Endocrinology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510100, China.
Jia-Lin LiaoDepartment of Endocrinology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510100, China.
David T W LuiDivision of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Ping ZhuDepartment of Endocrinology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510100, China. tanganqier@163.com.
Bin YaoAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China. hongyaobin_1212@tju.edu.cn.
Hai-Xia GuanDepartment of Endocrinology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510100, China. guanhaixia@gdph.org.cn.

Funding

Guangdong Provincial Special Support Program for Prominent Talents 2021JC06Y656National Key Research and Development Program of China 2022YFC2403100the Guangdong Major Project of Basic and Applied Basic Research 2023B0303000005
6 · The paper itself

Abstract

backgroundCardiovascular metabolic diseases (CMDs) are a major contributor to global mortality and disability, yet their pathogenesis remains incompletely understood, partly because existing in vitro models fail to capture disease complexity. Conventional engineered heart tissues (EHT), which typically contain only a limited set of cell types and lack neural components, cannot replicate the intricate neuro-cardiac interactions involved in CMDs.

objectiveThis study aimed to develop a neuron-like-Integrated Engineered Heart Tissue for investigating neuro-cardiac interactions under both physiological and pathological conditions, offering a new tool for CMD research.

methodsWe constructed a Sympathetic-like-Integrated Engineered Heart Tissue (SIEHT) by incorporating sympathetic-like neuronal cells into EHT. The structural and functional properties of SIEHT were systematically compared with conventional EHT using morphological analysis, immunofluorescence staining, contractility measurements, qPCR, and RNA sequencing. The model was then exposed to advanced glycation end products (AGEs) to assess pathological remodeling through multiple parameters, including cell viability, oxidative stress, structural and functional integrity, and transcriptomic profiles.

resultsSIEHT exhibited greater structural and functional maturation than EHT, as indicated by improved cardiomyocyte alignment, increased contraction amplitude, and upregulated expression of connexin 43. Transcriptomic analysis revealed enriched pathways associated with multi-system development. Under AGEs-induced pathological conditions, SIEHT demonstrated a more pronounced reduction in cell viability, elevated reactive oxygen species levels, more severe contractile dysfunction, a higher frequency of abnormal spontaneous beating, and greater neural injury relative to controls. Transcriptome profiling further identified significant enrichment of the AGE-RAGE signaling pathway in diabetic complications.

conclusionsWe successfully established a novel SIEHT model that recapitulates physiological neuro-cardiac interactions and AGEs-induced adverse remodeling across multiple dimensions, providing a powerful and innovative tool for elucidating the pathophysiological mechanisms of neuro-cardiac dysregulation in CMDs.

Indexed as

Glycation End Products, AdvancedMyocytes, CardiacNeuronsSympathetic Nervous SystemTissue EngineeringVentricular RemodelingAnimalsHumansMyocardial ContractionOxidative StressSignal TransductionTranscriptomeGlycation End Products, AdvancedAGEsCardiometabolic diseasesEngineered heart tissueInnervationiPSC-CM

Identifiers

PMID41535924
PMCPMC12888130

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.