Evidence map›Paper›PMID 41353685›Full record

ArticleAngiogenesis2025

Endothelial LRRC8A mitigates pressure overload-induced cardiac hypertrophy by promoting coronary angiogenesis.

Lingjun Jie, Baolong Feng, Yufan Zhou, Chan Du, Wenlin Zhou, Ruonan Zhang, Wei Shen, Jiajin Chen, Penglong Wu, Xu Kong and 6 more

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Angiogenesis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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

5 · Who and what money

Authors and funding

16 authors.

Lingjun Jie *Institute of Cardiovascular Diseases, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China. jie.lj@xmu.edu.cn.
Baolong Feng *Institute of Cardiovascular Diseases, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Yufan Zhou *Institute of Cardiovascular Diseases, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Chan Du *School of Medicine, Northwest University, Xi'an, Shanxi, China.
Wenlin ZhouInstitute of Cardiovascular Diseases, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Ruonan ZhangCollege of Life Sciences, China Jiliang University, Hangzhou, Zhejiang, China.
Wei ShenInstitute of Cardiovascular Diseases, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Jiajin ChenInstitute of Cardiovascular Diseases, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Penglong WuDepartment of Cardiology, School of Medicine, Xiamen Cardiovascular Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Xu KongXiamen Medical College Affiliated Haicang Hospital, Xiamen, Fujian, China.
Yuliang ZhanDepartment of Cardiology, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China.
Meimei ShiSchool of Medicine, Northwest University, Xi'an, Shanxi, China.
Guiyang LiDepartment of Cardiology, School of Medicine, Xiamen Cardiovascular Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China.
Lei LiThe Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Lei PanInstitute of Cardiovascular Diseases, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Yanhui ZhangInstitute of Cardiovascular Diseases, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.

Funding

National Natural Science Foundation of China 8227039 and 82000463Natural Science Fund of Fujian province 2023J011675Natural Science Fund of Fujian province 2024J011426Natural Science Fund of Xiamen Municipal Bureau of Science and Technology 3502Z20209150
6 · The paper itself

Abstract

objectiveClinical evidence has indicated that pressure overload-induced cardiac hypertrophy is closely linked with adverse cardiac outcomes. Endothelial dysfunction is a key contributor to the progression of cardiac hypertrophy and heart failure (HF). Although leucine-rich repeat-containing 8A (LRRC8A) serves as a critical regulator of vascular endothelial homeostasis, its functional role in pressure overload-induced pathological hypertrophy and dysfunction remains unclear. In this study, we aimed to investigate the role and mechanism of endothelial LRRC8A in pressure overload-induced pathological hypertrophy. METHODS AND

resultsHere, we found that LRRC8A expression was markedly downregulated in hypertrophic hearts and cardiac endothelial cells (CECs) from both patients and mice. Endothelial LRRC8A knockout mice exhibited exacerbated pathological hypertrophy and dysfunction following transverse aortic constriction (TAC) surgery. Moreover, single-cell RNA sequencing (scRNA-seq) analysis revealed that LRRC8A-deficient CECs displayed downregulation of gene programs related to angiogenesis, migration, and proliferation. Consistently, endothelial LRRC8A deficiency reduced capillary density in TAC hearts in vivo and inhibited endothelial cell (EC) tube formation, migration, and proliferation in vitro. Mechanistically, LRRC8A positively regulated the VEGF-VEGFR2 axis, interacted with VEGFR2, and promoted VEGFR2 endocytosis. Therapeutically, AAV9-ICAM2-LRRC8A gene therapy restored coronary angiogenesis and ameliorated TAC-induced hypertrophy and dysfunction.

conclusionOur findings identify endothelial LRRC8A as a critical regulator of coronary angiogenesis in pressure overload-induced hypertrophic hearts and indicate that it could serve as a therapeutic target for cardiac hypertrophy and HF.

Indexed as

CardiomegalyCoronary VesselsEndothelial CellsMembrane ProteinsNeovascularization, PathologicNeovascularization, PhysiologicAngiogenesisAnimalsHumansMaleMiceMice, Inbred C57BLMice, KnockoutVascular Endothelial Growth Factor Receptor-2Membrane ProteinsVascular Endothelial Growth Factor Receptor-2AngiogenesisCardiac hypertrophyEndotheliumHeart failureLRRC8A

Identifiers

PMID41353685

What OpenQuestion holds

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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.