Mechanisms of Periodic Acceleration Induced Endothelial Nitric Oxide Synthase (eNOS) Expression and Upregulation Using an In Vitro Human Aortic Endothelial Cell Model

Academic Article

Abstract

  • Following severe injury in cases like ischemia reperfusion, recovery and tissue repair are compromised due to microvascular failure. Nitric oxide (NO) has been shown to have both vasodilatory and anti-inflammatory effects, and to enhance recovery and tissue repair by increasing microcirculation. Therefore, techniques that induce endothelial derived nitric oxide (eNO) may provide a suitable supplemental treatment following injury. Periodic acceleration (pGz) applied to the supine positioned body in a repetitive head-foot direction increases pulsatile shear stress to the vascular endothelium. pGz provides cytoprotection in part because it increases expression of eNOS and eNOS phosphorylation (p-eNOS) in the heart and vasculature in models of whole body and focal ischemia reperfusion injuries in vivo. To confirm that endothelial cells are indeed the central mediator of NO production and to understand the signal transduction pathway through which pGz upregulates eNOS, we used an in vitro model of human aortic endothelial cells coated tubing, mimicking realistic conditions of blood vessels in vivo that are exposed to linear pulsatile flow (PF) or PF plus pGz (PF + pGz). PF + pGz produced significantly higher values of total eNOS and p-eNOS content than PF alone. Periodic acceleration also increased the ratio of phosphorylated Akt (p-Akt) to total Akt, as well as the ratio of p-ERK1/2 to total ERK1/2. Further, Wortmannin (PI3K inhibitor) inhibited phosphorylation of Akt and eNOS but not eNOS upregulation, while PD98059 (MEK inhibitor) inhibited phosphorylation of ERK1/2 and eNOS upregulation, but not eNOS phosphorylation. Therefore, this investigation shows that, pGz increases eNO and p-eNOS through the PI3K-Akt pathway and upregulated eNOS expression through the MEK-ERK1/2 pathway in cultured endothelial cells. © 2012 Biomedical Engineering Society.
  • Digital Object Identifier (doi)

    Author List

  • Wu H; Uryash A; Bassuk J; Kurlansky P; Giridharan GA; Shakeri M; Estrada R; Sethu P; Adams JA
  • Start Page

  • 292
  • End Page

  • 301
  • Volume

  • 3
  • Issue

  • 3