Time- and Dose-Dependent Effect of Dexamethasone on Endothelial Cell Apoptosis

Endothelial cell (EC) apoptosis plays a critical role in the physiological and pathological vascular regression, remodeling, and angiogenesis. There are several therapeutic agents such as glucocorticoids (GCs), which could influence EC apoptosis, causing coagulation events. Due to the paradoxical effects of GCs on cellular apoptosis, the aim of the current study was to investigate the dose and time in which GCs could initiate and terminate in vitro cellular apoptosis.

Dexamethasone (DEXA) was serially diluted 10-folds for 8 serial concentrations (from 1 mM to 0.1 nM) added to cultured human umbilical vein endothelial cells (HUVECs). The cytotoxic effects of DEXA on HUVEC were tested with a rapid colorimetric test using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. Apoptotic assays based on quantitative polymerase chain reaction was performed for Bax and Bcl-2 genes and terminal deoxynucleotidyl transferase dUTP nick end labeling assay.

DEXA at the concentration of 1 µM showed significant cytotoxic effects, more intense anti-apoptotic effects in lower concentrations (1 nM to 100 nM), and anti-apoptotic effects with less intensity in higher concentrations (10 µM to 1 mM). Six hours of treatment by 1 µM of DEXA was estimated as the initial time of DEXA that could remarkably induce HUVECs apoptosis. The maximum significant increase of apoptosis was detected 24 hours after treatment with DEXA.

Our findings suggested that GCs can influence cellular apoptosis in a dose- and time-dependent manner.