Evidence map›Paper›PMID 38346487›Full record

ArticleJournal of advanced research2025

Single-cell transcriptomic profiling of heart reveals ANGPTL4 linking fibroblasts and angiogenesis in heart failure with preserved ejection fraction.

Guoxing Li, Huilin Zhao, Zhe Cheng, Junjin Liu, Gang Li, Yongzheng Guo

Open access · goldAbstract read
In one paragraph

Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
11.3field-weighted citation impact, top 1% of its field
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

30 citing papers in PubMed, 28 citations in OpenAlex.

  1. Molecular Mechanisms Governing Vascular Function in Heart Failure.Arteriosclerosis, thrombosis, and vascular biology · 2026
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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

6 authors at 3 institutions in 1 country.

Guoxing LiInstitute of Life Sciences, Chongqing Medical University, 400016, China.
Huilin ZhaoInstitute of Life Sciences, Chongqing Medical University, 400016, China.
Zhe ChengDepartment of Cardiology, Chongqing University Three Gorges Hospital, Chongqing 404199, China.
Junjin LiuDepartment of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Gang LiInstitute of Life Sciences, Chongqing Medical University, 400016, China; Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, 400016, China. Electronic address: ligang@cqmu.edu.cn.
Yongzheng GuoDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: gyz_cardio@hospital.cqmu.edu.cn.
Chongqing Medical University · CNChongqing University · CNFirst Affiliated Hospital of Chongqing Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDespite the high morbidity and mortality, the effective therapies for heart failure with preserved fraction (HFpEF) are limited as the poor understand of its pathophysiological basis.

objectiveThis study was aimed to characterize the cellular heterogeneity and potential mechanisms of HFpEF at single-cell resolution.

methodsAn HFpEF mouse model was induced by a high-fat diet with N-nitro-L-arginine methyl ester. Cells from the hearts were subjected to single-cell sequencing. The key protein expression was measured with Immunohistochemistry and immunofluorescence staining.

resultsIn HFpEF hearts, myocardial fibroblasts exhibited higher levels of fibrosis. Furthermore, an increased number of fibroblasts differentiated into high-metabolism and high-fibrosis phenotypes. The expression levels of genes encoding certain pro-angiogenic secreted proteins were decreased in the HFpEF group, as confirmed by bulk RNA sequencing. Additionally, the proportion of the endothelial cell (EC) lineages in the HFpEF group was significantly downregulated, with low angiogenesis and high apoptosis phenotypes observed in these EC lineages. Interestingly, the fibroblasts in the HFpEF heart might cross-link with the EC lineages via over-secretion of ANGPTL4, thus displaying an anti-angiogenic function. Immunohistochemistry and immunofluorescence staining then revealed the downregulation of vascular density and upregulation of ANGPTL4 expression in HFpEF hearts. Finally, we predicted ANGPTL4as a potential druggable target using DrugnomeAI.

conclusionIn conclusion, this study comprehensively characterized the angiogenesis impairment in HFpEF hearts at single-cell resolution and proposed that ANGPTL4 secretion by fibroblasts may be a potential mechanism underlying this angiogenic abnormality.

Indexed as

Angiopoietin-Like Protein 4FibroblastsHeart FailureMyocardiumNeovascularization, PathologicNeovascularization, PhysiologicAngiogenesisAnimalsDisease Models, AnimalEndothelial CellsFibrosisGene Expression ProfilingHumansMaleMiceMice, Inbred C57BLAngiopoietin-Like Protein 4AngiogenesisANGPTL4HFpEFMetabolismscRNA-seq

Identifiers

PMID38346487
PMCPMC11785561
OpenAlexW4391826537

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.