Dr. Wayne Orr, assistant professor of pathology at the Louisiana State University Health Sciences Center, will give a talk Wednesday (Oct. 21) at 3:30 p.m. in Room 203 of the Zachry Engineering Center at Texas A&M University.

Orr’s talk, “CenterMatrix-specific signaling in shear stress-induced endothelial cell dysfunction,” is part of the Department of Biomedical Engineering’s seminar series.

Abstract
Endothelial cell dysfunction initiates early atherosclerotic plaque formation by promoting local LDL accumulation and facilitating leukocyte recruitment, whereas endothelial cell dysfunction in advanced plaques may contribute to thrombotic complications through enhanced endothelial cell turnover and leukocyte-dependent degradation of the plaque’s fibrotic cap. Regulation of endothelial cell dysfunction is multifactorial; classically ascribed to the combined effects of blood flow patterns and systemic risk factors. My research suggests that subendothelial matrix
composition is a novel regulator of endothelial cell dysfunction.

Shear stress, the frictional force generated by blood flow, activates the integrin family of extracellular matrix receptors resulting in enhanced receptor affinity, and matrix-specific integrin signaling alters the endothelial cell response to flow. Transitional matrix proteins, such as fibronectin and fibrinogen, accumulate in the subendothelial matrix early during endothelial cell dysfunction in vivo and prime endothelial cells for dysfunction in vitro by enhancing flow-induced permeability, proinflammatory signaling (NF-κB, JNK), and inflammatory gene expression. In contrast, basement membrane proteins are protective and limit flow-induced endothelial cell dysfunction. In this presentation, we will explore the mechanisms of the matrix-specific response to shear stress and examine the roles of p21 activated kinase (PAK) and protein kinase A (PKA) signaling in mediating this matrix-specific response.

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