Publication

Single-Cell RNA sequencing investigation of female-male differences under PAD conditions

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  • 06/25/2025
Type of Material
Authors
    Gloriani Sánchez Marrero, Emory UniversityNicolas Villa-Roel, Emory UniversityFeifei Li, Emory UniversityChristian Park, Emory UniversityDong-Won Kang, Emory UniversityKatherine Hekman Hekman, Emory UniversityHanjoong Jo, Emory UniversityLuke Brewster, Emory University
Language
  • English
Date
  • 2023-09-07
Publisher
  • Frontiers
Publication Version
Copyright Statement
  • © 2023 Sánchez Marrero, Villa-Roel, Li, Park, Kang, Hekman, Jo and Brewster.
License
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 10
Start Page
  • 1251141
Grant/Funding Information
  • This work was fully funded by the National Institutes of Health, grant HL143348.
Abstract
  • Peripheral arterial disease (PAD) is an age-related medical condition affecting mostly muscular arteries of the limb. It is the 3rd leading cause of atherosclerotic morbidity. The mechanical environment of endothelial cells (ECs) in PAD is characterized by disturbed blood flow (d-flow) and stiff extracellular matrices. In PAD, the stiffness of arteries is due to decreased elastin function and increased collagen content. These flow and stiffness parameters are largely missing from current models of PAD. It has been previously proven that ECs exposed to d-flow or stiff substrates lead to proatherogenic pathways, but the effect of both, d-flow and stiffness, on EC phenotype has not been fully investigated. In this study, we sought to explore the effect of sex on proatherogenic pathways that could result from exposing endothelial cells to a d-flow and stiff environment. We utilized the scRNA-seq tool to analyze the gene expression of ECs exposed to the different mechanical conditions both in vitro and in vivo. We found that male ECs exposed to different mechanical stimuli presented higher expression of genes related to fibrosis and d-flow in vitro. We validated our findings in vivo by exposing murine carotid arteries to d-flow via partial carotid artery ligation. Since women have delayed onset of arterial stiffening and subsequent PAD, this work may provide a framework for some of the pathways in which biological sex interacts with sex-based differences in PAD.
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Research Categories
  • Health Sciences, Medicine and Surgery

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