Results
To test our hypothesis, ACE-2 expression was evaluated in cultured
HUVECs treated with clinically relevant dose 5mM of VPA[19, 21] for
24 hours. HUVECs represent the standard cellular model to study
endothelial cells in vitro .[19, 20, 22] Our qPCR data
demonstrated a significant ~70% reduction in the
expression level of ACE-2 in VPA-treated ECs in comparison to control
ECs (Fig. 1A ). Given the venous nature of HUVECs, we next
evaluated the expression level of ACE-2 in an arterial ECs by treating
cultured HCAECs with 5mM of VPA for 24 hours. Similar to HUVECs, we
observed a significant ~70% reduction in the ACE-2
expression in VPA-treated in comparison to vehicle-treated control
HCAECs (Fig. 1B ). To assess dose-response effect of higher dose
of VPA on endothelial ACE-2 expression, we treated HUVECs with 10mM and
20mM of VPA for 24 hours and evaluated ACE-2 expression. Our qPCR data
showed a significant reduction in ACE-2 expression for both 10 mM and 20
mM of VPA but there was no difference in ACE-2 expression between 10 and
20 mM of VPA treated ECs. Next, we evaluated the effect of VPA on
pro-inflammatory IL-6 expression, and endothelial activation marker
ICAM-1 expression. We observed a significant down-regulation of IL-6
following 5mM of VPA treatment to HUVECs in comparison to control
(Fig. 1C, D ). Interestingly, VPA also significantly reduced
ICAM-1 expression in VPA-treated in comparison to control ECs
(Fig. 1E ).