Contributions of an Extracellular Matrix Glycoprotein to Coronary Vessel Formation

Location

Philadelphia, PA

Start Date

9-5-2018 1:00 PM

Description

Introduction: Elucidation of the mechanisms that govern nascent coronary vessel formation is required to therapeutically regrow malformed vessels. Embryonic mice with epicardial-specific deletion of Tbx5 (Tbx5epi-/-) exhibit punctate cardiac hemorrhaging. Reln mRNA encodes the Reelin extracellular matrix glycoprotein and is reduced in embryonic Tbx5epi-/- mouse hearts. Therefore, expression of Reelin in coronary vascular endothelial cells may be critical for establishing vascular integrity.

Study Objective: The goal of this study was to elucidate contributions of Reelin to endothelial cell function.

Methods: We utilized human dermal microvascular endothelial cells (HDMECs) to assess contributions of Reelin to endothelial cell function. We achieved RELN gene silencing through a small interfering RNA-mediated approach that led to >90% reduction in both RELN mRNA and Reelin protein expression. Control and RELN-silenced endothelial cells were then subjected to assays that examined adherence and the permeability of HDMEC monolayers grown on semi-porous membranes.

Results: Our results indicate that RELN silencing alters in vitro endothelial cell adhesion and cell membrane permeability.

Conclusions: We conclude that Reelin plays a critical role during coronary vessel development as it regulates the establishment of vascular integrity through regulation of cell adhesions and membrane permeability.

Embargo Period

5-30-2018

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COinS
 
May 9th, 1:00 PM

Contributions of an Extracellular Matrix Glycoprotein to Coronary Vessel Formation

Philadelphia, PA

Introduction: Elucidation of the mechanisms that govern nascent coronary vessel formation is required to therapeutically regrow malformed vessels. Embryonic mice with epicardial-specific deletion of Tbx5 (Tbx5epi-/-) exhibit punctate cardiac hemorrhaging. Reln mRNA encodes the Reelin extracellular matrix glycoprotein and is reduced in embryonic Tbx5epi-/- mouse hearts. Therefore, expression of Reelin in coronary vascular endothelial cells may be critical for establishing vascular integrity.

Study Objective: The goal of this study was to elucidate contributions of Reelin to endothelial cell function.

Methods: We utilized human dermal microvascular endothelial cells (HDMECs) to assess contributions of Reelin to endothelial cell function. We achieved RELN gene silencing through a small interfering RNA-mediated approach that led to >90% reduction in both RELN mRNA and Reelin protein expression. Control and RELN-silenced endothelial cells were then subjected to assays that examined adherence and the permeability of HDMEC monolayers grown on semi-porous membranes.

Results: Our results indicate that RELN silencing alters in vitro endothelial cell adhesion and cell membrane permeability.

Conclusions: We conclude that Reelin plays a critical role during coronary vessel development as it regulates the establishment of vascular integrity through regulation of cell adhesions and membrane permeability.