Abstract 151: ZBTB46 is a Shear Stress Sensitive Transcription Factor in Endothelial Cells
Background: ZBTB46, also known as zDC or BTBD4, is a member of the BTB-ZF protein family which comprises a diverse group of transcription factors. Recently, ZBTB46 was identified as a transcription repressor specific to classical dendritic cells (cDCs) among immune cells and responsible for keeping cDCs in a quiescent state. ZBTB46 down-regulation by TLR signaling leads to cDC activation. Interestingly, endothelial cells also express ZBTB46, and may be viewed as part of the immune system; expressing functional TLRs and interacting with other immune cells. However, the role of ZBTB46 in endothelial cells has not been studied. Endothelial cell activation in areas of disturbed flow is a critical step in initiation of atherosclerosis, leading to heart attacks and stroke.
Hypothesis: ZBTB46 is expressed in quiescent endothelial cells under laminar shear conditions and is down-regulated by low and oscillatory shear stress patterns as seen in areas of disturbed flow, leading to endothelial cell activation.
Methods: We used the mouse partial carotid ligation model to assess ZBTB46 shear responsiveness in vivo and a cone and plate cell culture model to assess shear responsiveness in vitro. We measured endothelial cell mRNA using qPCR and protein via western blot. We used immunofluorescence to show localization of ZBTB46 in the arterial wall.
Results: We showed that ZBTB46 is expressed in both human and mouse endothelial cells by mRNA and protein measurements. We also showed that ZBTB46 is down-regulated under low and oscillatory shear conditions after 48 hours both in vivo (Figure 1-A) and in vitro (Figure 1-B). Further functional studies including monocyte adhesion and migration assays as well as mechanistic studies assessing upstream and downstream pathways are currently underway.
Author Disclosures: A. Rezvan: None. H. Sun: None. H. Jo: None.
- © 2014 by American Heart Association, Inc.