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Isolation of Primary Mouse Lung Endothelial Cells
06:41

Isolation of Primary Mouse Lung Endothelial Cells

Published on: November 10, 2021

Pulmonary endothelial cell signaling and function

Sharon Rounds1, Qing Lu, Elizabeth O Harrington

  • 1Vascular Research Laboratory, Department of Medicine, Warren Alpert Medical School of Brown University, Providence VA Medical Center, Providence, Rhode Island 02903, USA. sharon_rounds@brown.edu

Transactions of the American Clinical and Climatological Association
|July 4, 2008
PubMed

Insights

Inhibiting RhoA carboxyl methylation reduces endothelial permeability. Enhancing this methylation increases permeability, suggesting therapeutic potential for vascular diseases by modulating intracellular adenosine.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Physiology

Background:

  • Endothelial monolayer permeability is crucial for vascular function.
  • Posttranslational modifications, like carboxyl methylation, regulate small GTPases (e.g., RhoA).
  • RhoA activity influences endothelial barrier integrity.

Purpose of the Study:

  • To investigate the role of RhoA carboxyl methylation in endothelial monolayer permeability.
  • To explore the therapeutic potential of modulating this pathway.

Main Methods:

  • Utilized chemical inhibitors (adenosine plus homocysteine, N-acetyl-S-geranylgeranyl-L-cysteine) of isoprenylcysteine-O-carboxyl methyltransferase (ICMT).
  • Generated stable cell lines overexpressing ICMT in bovine pulmonary artery endothelial cells (BPAEC).
  • Assessed RhoA methylation and activation, and measured monolayer permeability.
  • Investigated the effect of an adenosine deaminase inhibitor on lung edema.

Main Results:

  • Inhibition of ICMT decreased RhoA methylation and activation, correlating with reduced BPAEC monolayer permeability.
  • Overexpression of ICMT in BPAEC enhanced monolayer permeability, linked to increased RhoA methylation and activation.
  • Adenosine deaminase inhibition attenuated and rescued lung edema.

Conclusions:

  • ICMT modulates endothelial monolayer permeability by regulating RhoA carboxyl methylation and activation.
  • Increasing intracellular adenosine may be a therapeutic strategy for diseases involving increased vascular permeability.
Keywords:
RhoAadenosinecarboxyl methylationedemaendothelial monolayer permeability

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