Evidence map›Paper›PMID 41311910›Full record

ArticleJVS-vascular science2025

Piezo-type mechanosensitive ion channel component 1 (PIEZO1) is upregulated in peripheral arterial disease (PAD) and a novel murine PAD model.

Fujie Zhao, Feifei Li, Farbod Sedaghati, Hai Dong, Sandeep Kumar, Dennis Gene Foster, Jim Otto, Dana Giangiacomo, Lucas H Timmins, Maiko Sasaki and 9 more

Abstract read
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In one paragraph

Article in JVS-vascular science, 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

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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

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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

19 authors.

Fujie ZhaoDepartment of Surgery, Emory University School of Medicine, Atlanta, GA.
Feifei LiDepartment of Surgery, Emory University School of Medicine, Atlanta, GA.
Farbod SedaghatiThe George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA.
Hai DongDepartment of Surgery, Emory University School of Medicine, Atlanta, GA.
Sandeep KumarBME Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA.
Dennis Gene FosterDepartment of Surgery, Emory University School of Medicine, Atlanta, GA.
Jim OttoDepartment of Surgery, Duke University, Durham, NC.
Dana GiangiacomoDepartment of Surgery, Duke University, Durham, NC.
Lucas H TimminsDepartment of Biomedical Engineering, Texas A&M University, Houston, TX.
Maiko SasakiDepartment of Surgery, Emory University School of Medicine, Atlanta, GA.
Gloriani Sanchez MarreroDepartment of Surgery, Emory University School of Medicine, Atlanta, GA.
Kyung In BaekBME Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA.
Michael TuDepartment of Surgery, Emory University School of Medicine, Atlanta, GA.
Sandra PeprahDepartment of Surgery, Emory University School of Medicine, Atlanta, GA.
Xiangqin CuiDepartment of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA.
Jeffrey H LawsonDepartment of Surgery, Duke University, Durham, NC.
Rudolph L GleasonThe George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA.
Hanjoong JoBME Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA.
Luke BrewsterDepartment of Surgery, Emory University School of Medicine, Atlanta, GA.

Funding

Molecular Mechanisms of Flow-dependent Arterial Remodeling in Peripheral Arterial DiseaseR01HL143348 · NHLBI · EMORY UNIVERSITY · PI BREWSTER, LUKE PACKARD · 2018 to 2022
$3.6M
NHLBI NIH HHS R01 HL143348
6 · The paper itself

Abstract

Objective: The objectives of this work are to: define murine femoral artery stiffening with age and the modifiability of this process by exercise; impose peripheral arterial disease (PAD) hemodynamics on murine femoral arteries and to deliver focal atherosclerotic plaque to femoral arteries; and test piezo-type mechanosensitive ion channel component 1 (PIEZO1) expression in human and murine femoral arteries of PAD. Methods: We used a running wheel to exercise young and old S129 mice and biomechanical testing to quantify changes in arterial stiffness. We created a novel partial femoral artery ligation (PFL) model to impose PAD hemodynamics via low wall shear stress (WSS) to create a flow-mediated model of arterial aging in femoral arteries. In vivo mechanics were defined with ultrasound. Ex vivo arteries underwent biaxial tests. Atherogenic conditions were induced using PCSK9 infection and a high-fat diet. Arterial remodeling and PIEZO1 expression were quantified by histology. Results: Femoral arteries are naturally stiffer than carotid arteries; both stiffen further with aging, but exercise improved compliance in old femoral arteries. PFL imposed low WSS and stiffening, similar to that seen in aging. Under atherogenic conditions, PFL delivered focal atherosclerotic plaques in femoral arteries. Low WSS increased PIEZO1 expression in femoral arteries (∼1.8× in endothelial cells, ∼2.4× in smooth muscle cells, and ∼2.8× in macrophages). Human PAD arteries with high-grade stenosis validated increased PIEZO1 mRNA (∼1.83×). Conclusions: Femoral artery mechanics differ significantly from the carotid artery but can be modified by exercise. This PFL model confers arterial stiffness, and under atherogenic conditions, delivers focal femoral atherosclerotic plaque. PIEZO1 expression increases in both PFL-treated mouse femoral arteries and human PAD arteries with severe stenosis, supporting this as a translational target for PAD. Clinical Relevance: Peripheral artery disease (PAD) is the third most common atherosclerotic bed. PAD is associated with increased risk of limb loss and death, but the mechanisms driving site-specific arterial remodeling in PAD remain unclear. This work uniquely creates a model of PAD that incorporates arterial stiffening via aging and flow disturbances and inducing atherosclerotic plaque into the murine femoral artery. By comparing murine femoral arteries with PAD arteries, piezo-type mechanosensitive ion channel component 1 (PIEZO1) was discovered as key mediator linking PAD blood flow and stiffening to untoward changes in endothelial cells, smooth muscle cells, and macrophages within femoral arteries. Targeted modulation of PIEZO1 activity provide PAD-centric therapeutic strategies and help promote the vascular health, life, and limb outcomes in patients with PAD.

Indexed as

Atherosclerotic plaqueFemoral arteryMechanosensitive ion channelsPeripheral arterial diseasePIEZO1

Identifiers

PMID41311910
PMCPMC12648979

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.