Primary African American endothelial cells exhibit endothelial dysfunction with an exacerbated inflammatory profile and blunted MMP-2 activity

Marc D. Cook, Chenyi Ling, Heather Grimm, Adelola Adeyemo, Maitha Aldokhayyil, Kevin Heffernan, Bo Fernhall, Michael Brown

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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)-1b 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.

Original languageEnglish (US)
Pages (from-to)38-46
Number of pages9
JournalArtery Research
Volume27
Issue number1
DOIs
StatePublished - Mar 2021

Keywords

  • Endothelial dysfunction
  • Hypertension
  • Inflammation
  • Matrix metalloproteinase-2
  • Racial difference

ASJC Scopus subject areas

  • Anatomy
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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