Constant or fluctuating hyperglycemias increases cytomembrane stiffness of human umbilical vein endothelial cells in culture: roles of cytoskeletal rearrangement and nitric oxide synthesis

BackgroundPrevious studies have implicated continuous or intermittent hyperglycemia in altered endothelium-derived nitric oxide (NO) synthesis. NO can regulate both the F-actin cytoskeleton and endothelial cell membrane stiffness. Atomic force microscopy (AFM) is a powerful tool that can be used to study plasma membrane deformability at the single cell level. As membrane stiffness is partially dependent on filamentous F-actin, the interdependence of these parameters can be studied through the combined approaches of AFM and laser scanning confocal microscopy (LSCM). In the present study, we evaluated the effects of constant or fluctuating hyperglycemia on endothelial-derived NO synthesis, the cytoskeletal contribution and endothelial cell membrane stiffness.ResultsCompared to control cells cultured in low glucose (5 mM), constant (25 mM) or fluctuating (25/5 mM) high glucose significantly decreased NO release along with stiffening of endothelial cell membranes and F-actin rearrangement. The non-selective nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) exerted similar effects on endothelial cells. Increasing concentrations of L-NAME (from 0.1 to 1 mM) exacerbated these effects in a concentration-dependent manner.ConclusionsResult from the present study suggest that stiffening endothelial cell membranes are associated with decreased NO synthesis, which was established through the F-actin cytoskeletal redistribution. The precise mechanisms of hyperglycemia-induced endothelial dysfunction require further investigation.

• Publication year

  2013

• Venue

  BMC Cell Biology

• Publication date

  2013-04-22

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1186/1471-2121-14-22PMID 23601245PMCID 3651398
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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