title: Modulation of endothelial cell integrity and inflammatory activation by commercial lipid emulsions.
abstract: BACKGROUND
  Thrombosis and immune dysfunction are two important complications that result from the administration of parenteral nutrition. Endothelial cells within the vasculature are crucial components necessary for maintenance of normal coagulation and immune function.
  
  
  METHODS
  We compared the effects of three commercial lipid emulsions (LEs; Intralipid®, ClinOleic® [or Clinolipid®], and Omegaven®) differing in the levels of omega-6 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, omega-9 monounsaturated fatty acids, and saturated fatty acids upon endothelial cell fatty acid composition using Gas chromatography, endothelial cell integrity by assessing measurement of apoptosis and necrosis using flow cytometry, endothelial cell inflammatory activation by assessing the induction of ICAM-1 by lipopolysaccharide [LPS]), and transcription factor activation (phosphorylation of NF-κB) using western blot analysis.
  
  
  RESULTS
  Gas chromatographic analysis confirmed cellular uptake of the fatty acids within the LEs; furthermore, these fatty acid changes reflected the composition of the oils and egg phosphatides used in the manufacturing of these emulsions. However, the kinetics of fatty acid uptake and processing differed between LEs. Fish oil LE negatively impacted cell viability by doubling the percentage of apoptotic and necrotic cell populations quantified by flow cytometry using Annexin V/Fluorescein and propidium iodide. The soybean oil LE did not alter cell viability, while the olive oil-predominate emulsion improved cell viability. All LEs were capable of suppressing LPS-induced ICAM-1 expression; however, the fish oil LE was more potent than the other emulsions. Fish oil LE supplementation of cells also suppressed LPS-induced phosphorylation of NF-κB, while the soybean oil and olive predominant LE had no effect upon NF-κB phosphorylation.
  
  
  CONCLUSIONS
  Lipid emulsions are readily incorporated and stored in the form of triacylglycerols. Soybean oil-based, olive oil-predominant and fish-oil based LEs differentially affected endothelial cell integrity. Importantly, these three LEs were capable of suppressing endothelial cell inflammatory response despite their fatty acid content.
authors.affiliation: Cellular Biochemistry Laboratory, Methodist Research Institute, Indiana University Health, 1800 N. Capitol Ave, E504D, Indianapolis, IN, 46202, USA. kharvey@iuhealth.org.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Harvey
authors.affiliation: Cellular Biochemistry Laboratory, Methodist Research Institute, Indiana University Health, 1800 N. Capitol Ave, E504D, Indianapolis, IN, 46202, USA. zxu@iuhealth.org.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Baxter Healthcare Corporation, Deerfield, IL, 60015, USA. tom_pavlina@yahoo.com.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Pavlina
authors.affiliation: Baxter Healthcare Corporation, Deerfield, IL, 60015, USA. gary_zaloga@baxter.com.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Zaloga
authors.affiliation: Cellular Biochemistry Laboratory, Methodist Research Institute, Indiana University Health, 1800 N. Capitol Ave, E504D, Indianapolis, IN, 46202, USA. rsiddiqu@iuhealth.org.|Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. rsiddiqu@iuhealth.org.
authors.forename: Rafat A
authors.initials: RA
authors.lastname: Siddiqui
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005217:Fat Emulsions, Intravenous / Q000737:chemistry / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016328:NF-kappa B / Q000032:analysis; D010743:Phospholipids / Q000032:analysis; D014280:Triglycerides / Q000032:analysis
chemical_list: D005217:Fat Emulsions, Intravenous; D005227:Fatty Acids; D016328:NF-kappa B; D010743:Phospholipids; D014280:Triglycerides; D018799:Intercellular Adhesion Molecule-1