The Glycocalyx and Pressure-Dependent Transcellular Albumin Transport

Randal O. Dull, Andreia Z. Chignalia

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Purpose: Acute increases in hydrostatic pressure activate endothelial signaling pathways that modulate barrier function and vascular permeability. We investigated the role the glycocalyx and established mechanotransduction pathways in pressure-induced albumin transport across rat lung microvascular endothelial cells. Methods: Rat lung microvascular endothelial cells (RLMEC) were cultured on Costar Snapwell chambers. Cell morphology was assessed using silver nitrate staining. RLMEC were exposed to zero pressure (Control) or 30 cmH2O (Pressure) for 30 or 60 min. Intracellular albumin uptake and transcellular albumin transport was quantified. Transcellular transport was reported as solute flux (Js) and an effective permeability coefficient (Pe). The removal of cell surface heparan sulfates (heparinase), inhibition of NOS (L-NAME) and reactive oxygen species (apocynin, Apo) was investigated. Results: Acute increase in hydrostatic pressure augmented albumin uptake by 30–40% at 60 min and Js and Pe both increased significantly. Heparinase increased albumin uptake but attenuated transcellular transport while L-NAME attenuated both pressure-dependent albumin uptake and transport. Apo interrupted albumin uptake under both control and pressure conditions, leading to a near total lack of transcellular transport, suggesting a different mechanism and/or site of action. Conclusion: Pressure-dependent albumin uptake and transcellular transport is another component of endothelial mechanotransduction and associated regulation of solute flux. This novel albumin uptake and transport pathway is regulated by heparan sulfates and eNOS. Albumin uptake is sensitive to ROS. The physiological and clinical implications of this albumin transport are discussed.

Original languageEnglish (US)
Pages (from-to)655-662
Number of pages8
JournalCardiovascular Engineering and Technology
Volume11
Issue number6
DOIs
StatePublished - Dec 2020
Externally publishedYes

Keywords

  • Caveolea
  • Endothelium
  • Heparan sulfate
  • Permeability
  • Transcytosis
  • eNOS

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cardiology and Cardiovascular Medicine

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