title: High-density lipoprotein 3 and apolipoprotein A-I alleviate platelet storage lesion and release of platelet extracellular vesicles.
abstract: BACKGROUND
  Stored platelet (PLT) concentrates (PLCs) for transfusion develop a PLT storage lesion (PSL), decreasing PLT viability and function with profound lipidomic changes and PLT extracellular vesicle (PL-EV) release. High-density lipoprotein 3 (HDL3 ) improves PLT homeostasis through silencing effects on PLT activation in vivo. This prompted us to investigate HDL3 and apolipoprotein A-I (apoA-I) as PSL-antagonizing agents.
  
  
  METHODS
  Healthy donor PLCs were split into low-volume standard PLC storage bags and incubated with native (n)HDL3 or apoA-I from plasma ethanol fractionation (precipitate IV) for 5 days under standard blood banking conditions. Flow cytometry, Born aggregometry, and lipid mass spectrometry were carried out to analyze PL-EV release, PLT aggregation, agonist-induced PLT surface marker expression, and PLT and plasma lipid compositions.
  
  
  RESULTS
  Compared to control, added nHDL3 and apoA-I significantly reduced PL-EV release by up to -62% during 5 days, correlating with the added apoA-I concentration. At the lipid level, nHDL3 and apoA-I antagonized PLT lipid loss (+12%) and decreased cholesteryl ester (CE)/free cholesterol (FC) ratios (-69%), whereas in plasma polyunsaturated/saturated CE ratios increased (+3%) and CE 16:0/20:4 ratios decreased (-5%). Administration of nHDL3 increased PLT bis(monoacylglycero)phosphate/phosphatidylglycerol (+102%) and phosphatidic acid/lysophosphatidic acid (+255%) ratios and improved thrombin receptor-activating peptide 6-induced PLT aggregation (+5%).
  
  
  CONCLUSIONS
  nHDL3 and apoA-I improve PLT membrane homeostasis and intracellular lipid processing and increase CE efflux, antagonizing PSL-related reduction in PLT viability and function and PL-EV release. We suggest uptake and catabolism of nHDL3 into the PLT open canalicular system. As supplement in PLCs, nHDL3 or apoA-I from Fraction IV of plasma ethanol fractionation have the potential to improve PLC quality to prolong storage.
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, Regensburg, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Pienimaeki-Roemer
authors.forename: Astrid
authors.initials: A
authors.lastname: Fischer
authors.forename: Maria
authors.initials: M
authors.lastname: Tafelmeier
authors.forename: Evelyn
authors.initials: E
authors.lastname: Orsó
authors.forename: Tatiana
authors.initials: T
authors.lastname: Konovalova
authors.forename: Alfred
authors.initials: A
authors.lastname: Böttcher
authors.forename: Gerhard
authors.initials: G
authors.lastname: Liebisch
authors.forename: Armin
authors.initials: A
authors.lastname: Reidel
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
mesh_terms: D016632:Apolipoprotein A-I / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D001793:Blood Preservation / Q000009:adverse effects; D002470:Cell Survival / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D053440:Lipoproteins, HDL3 / Q000494:pharmacology*; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010979:Platelet Function Tests; D053657:Platelet-Rich Plasma
chemical_list: D016632:Apolipoprotein A-I; D053440:Lipoproteins, HDL3; D010975:Platelet Aggregation Inhibitors