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

Authors

Marc D. Cook^{1, 7, *,} , Chenyi Ling^2, , Heather Grimm³, Adelola Adeyemo^6, , Maitha Aldokhayyil^4, , Kevin Heffernan⁶, Bo Fernhall⁷, Michael Brown^{4, 7}

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

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

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

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

⁵School of Medicine-Geriatrics, University of Utah, Salt Lake City, UT, USA

⁶Department of Exercise Science, Syracuse University, Syracuse, NY, USA

⁷Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, USA

^*Corresponding author. Email: mdcook@ncat.edu

DOI

10.2991/artres.k.201102.005How to use a DOI?

Keywords

Endothelial dysfunction; hypertension; inflammation; matrix metalloproteinase-2; racial difference

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.

Copyright

© 2020 Association for Research into Arterial Structure and Physiology. Publishing services by Atlantis Press International B.V.

Open Access

This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

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TY  - JOUR
AU  - Marc D. Cook
AU  - Chenyi Ling
AU  - Heather Grimm
AU  - Adelola Adeyemo
AU  - Maitha Aldokhayyil
AU  - Kevin Heffernan
AU  - Bo Fernhall
AU  - Michael Brown
PY  - 2020
DA  - 2020/11/18
TI  - Primary African American Endothelial Cells Exhibit Endothelial Dysfunction with an Exacerbated Inflammatory Profile and Blunted MMP-2 Activity
JO  - Artery Research
SP  - 38
EP  - 46
VL  - 27
IS  - 1
SN  - 1876-4401
UR  - https://doi.org/10.2991/artres.k.201102.005
DO  - 10.2991/artres.k.201102.005
ID  - Cook2020
ER  -