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

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)-1 beta 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. (C) 2020 Association for Research into Arterial Structure and Physiology. Publishing services by Atlantis Press International B.V.

Automated summary

Endothelial dysfunction is associated with racial health disparity in vascular dysfunction in African Americans. MMP-2 expression in endothelial cells has been linked to hypertension, with AA HUVEC showing higher basal MMP-2 expression but lower secreted MMP-2 activity compared to CA HUVEC. Inflammatory stimuli worsened relative MMP-2 activity in AA HUVEC.