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Primary African American Endothelial Cells Exhibit Endothelial Dysfunction with an Exacerbated Inflammatory Profile and Blunted MMP-2 Activity

Artery Research volume 27, pages 38–46 (2021)Cite this article

Abstract

Endothelial dysfunction is associated with the racial health disparity in vascular dysfunction in African Americans (AAs). Matrix Metalloproteinase (MMP)-2 is constitutively expressed in endothelial cells (EC) and is a biomarker that has been associated with hypertension, as its properties are involved in pathologic oxidative stress and pro-inflammation that may affect vascular homeostasis. Herein, we report significant inverse relationships between MMP-2, stroke volume, carotid and aortic systolic pressures in a small cohort of young AA men. In the current study, we postulated that basal activation in AA Endothelial Cells (EC) may include different responses in MMP-2 activity, compared to Caucasian (CA). We evaluated gene and protein expression and activity of MMP-2, and related peptides, in multiple different primary Human Umbilical Vein Endothelial Cells (HUVEC) isolated from four different AA and CA donors. Compared to CA, AA HUVEC exhibited greater basal MMP-2, MMP-14, Tissue inhibitor of metalloproteinase-2, Vascular cell adhesion molecule-1, Intracellular adhesion molecule-1, and Interleukin (IL)-1β gene expression and greater endothelin-1 secretion (p < 0.05). Interestingly, basal MMP-2 protein expression was greater while relative secreted MMP-2 activity was lower (p = 0.041). Inflammatory stimuli (tumor necrosis factor-alpha) exacerbated relative MMP-2 activity in AA HUVEC (p = 0.007). These in vitro data offer insights into a potential mechanism involving primary endothelial cell inflammatory mediated MMP-2 activities that may contribute to poorer vascular outcomes. Further studies are necessary to investigate endothelial intracellular transcriptional, translational, and activity regulation of MMP-2.

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Authors and Affiliations

  1. Department of Kinesiology, North Carolina Agricultural and Technical State University, Greensboro, NC, USA

    Marc D. Cook

  2. Department of Biology, University of Alaska, Fairbanks, AK, USA

    Chenyi Ling

  3. Department of Exercise Science, Kings College, Wilkes-Barre, PA, USA

    Heather Grimm

  4. School of Kinesiology, Auburn University, Auburn, AL, USA

    Maitha Aldokhayyil & Michael Brown

  5. Department of Exercise Science, Syracuse University, Syracuse, NY, USA

    Adelola Adeyemo & Kevin Heffernan

  6. Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, USA

    Marc D. Cook, Bo Fernhall & Michael Brown

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  1. Marc D. Cook
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Correspondence to Marc D. Cook.

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Peer review under responsibility of the Association for Research into Arterial Structure and Physiology

Data availability statement: The data used to support the findings of this study are available from the corresponding author upon request.

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Cook, M.D., Ling, C., Grimm, H. et al. Primary African American Endothelial Cells Exhibit Endothelial Dysfunction with an Exacerbated Inflammatory Profile and Blunted MMP-2 Activity. Artery Res 27, 38–46 (2021). https://doi.org/10.2991/artres.k.201102.005

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  • DOI: https://doi.org/10.2991/artres.k.201102.005

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Artery Research

ISSN: 1876-4401

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