title: Digoxin immune fab protects endothelial cells from ouabain-induced barrier injury.
abstract: PROBLEM  Endogenous digitalis-like factors (EDLF) inhibit sodium pump Na(+) /K(+) ATPase activity, and maternal EDLF levels are elevated in preeclampsia (PE). This study determined whether digoxin immune Fab (DIF) could protect endothelial cells (ECs) from EDLF-induced endothelial barrier dysfunction. METHOD OF STUDY  ECs were treated with escalating doses of ouabain (a known EDLF) in the presence or absence of DIF. EC barrier integrity was examined by junction protein VE-cadherin and occludin expressions. EC permeability was determined by horseradish-peroxidase (HRP) leakage and transendothelial electrical resistance (TEER). RESULTS  EC junction protein VE-cadherin distribution was disrupted in cells treated with ouabain. DIF, but not control IgG Fab fragment, blocked ouabain-induced decreases in VE-cadherin and occludin expressions and prevented ouabain-induced HRP leakage and TEER changes. CONCLUSION  DIF protects ECs from ouabain-induced barrier injury, providing evidence of beneficial effects of DIF on EC function and supporting that Na(+) /K(+) ATPase might be a therapeutic target to ameliorate endothelial dysfunction.
authors.affiliation: Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center (LSUHSC), Shreveport, USA. ywang1@lsuhsc.edu
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wang
authors.forename: Ruping
authors.initials: R
authors.lastname: Fan
authors.forename: Yang
authors.initials: Y
authors.lastname: Gu
authors.forename: C David
authors.initials: CD
authors.lastname: Adair
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000276:immunology; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006735:Horseradish Peroxidase / Q000032:analysis; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D062793:Occludin; D010042:Ouabain / Q000009:adverse effects*; D011225:Pre-Eclampsia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D015820:Cadherins; D006735:Horseradish Peroxidase; D007140:Immunoglobulin Fab Fragments; D008565:Membrane Proteins; D062793:Occludin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D000099152:Cadherin 5; C568985:OCLN protein, human; C050199:digoxin antibodies Fab fragments