Effect of albumin solutions on endothelial oxidant injury: A microfluidic study

Published:November 11, 2022DOI:



      Studies have suggested a beneficial effect of early plasma-based resuscitation in patients following trauma-hemorrhagic shock. The underlying mechanism(s) are unknown but may be owing to protective effects of plasma components on the endothelium and its glycocalyx layer. Albumin, the major protein in plasma, influences vascular integrity and has antioxidant properties in vivo. Sphingosine 1-phosphate is a bioactive sphingolipid with diverse signaling functions, which include endothelial barrier protection in part owing to preservation of the glycocalyx. Sphingosine 1-phosphate is bound mainly to albumin and high-density lipids in the plasma. Debate continues about the beneficial effect of albumin solutions in shock resuscitation. Pharmacologic preparations may modify constituents of albumin solutions for clinical use. We examined the relative effects of sphingosine 1-phosphate concentrations in albumin solutions on the endothelial-glycocalyx barrier in an in vitro microfluidic platform.


      Endothelial cell monolayers were established in microfluidic perfusion devices and exposed to control or biomimetic shock conditions followed by 5% plasma or different albumin solutions ± exogenous sphingosine 1-phosphate perfusion. Biomarkers of endothelial and glycocalyx activation, damage, and oxidant injury were then determined.


      Endothelial cell and glycocalyx barriers were damaged after biomimetic shock conditions. Plasma and sphingosine 1-phosphate loaded albumin solutions protected against barrier injury. Modest protective effects were noted with albumin alone; the efficacy varied with sphingosine 1-phosphate content of the albumin solution.


      The protective effect of albumin on the endothelia-glycocalyx barrier against oxidant injury was dependent on its sphingosine 1-phosphate concentration. Our data may help explain the discrepancies regarding the effectiveness of albumin solutions in shock resuscitation.
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        • Pusateri A.E.
        • Moore E.E.
        • Moore H.B.
        • et al.
        Association of prehospital plasma transfusion with survival in trauma patients with hemorrhagic shock when transport times are longer than 20 minutes.
        JAMA Surg. 2020; 155e195085
        • Diebel M.E.
        • Diebel L.N.
        • Liberati D.M.
        Protective effects of plasma products on the endothelial-glycocalyx barrier following trauma-hemorrhagic shock: is sphingosine-1 phosphate responsible?.
        J Trauma Acute Care Surg. 2019; 87: 1061-1069
        • Abassi Z.
        • Armaly Z.
        • Heyman S.M.
        Glycocalyx degradation in ischemia-reperfusion injury.
        Am J Pathology. 2020; 190: 752-767
        • Johansson P.
        • Stensballe J.
        • Ostrowski S.
        Shock induced endotheliopathy (SHINE) in acute critical illness-a unifying pathophysiologic mechanism.
        Critical Care. 2017; 21: 25
        • Garcia de Lomana A.L.
        • Vilhjalmsson A.I.
        • et al.
        Metabolic response in endothelial cells to catecholamine stimulation associated with increased vascular permeability.
        Int J Mol Sci. 2022; 23: 3162
        • Ali M.M.
        • Mahmoud A.M.
        • Le Master E.
        • Leviton I.
        • Phillips S.A.
        Role of matrix metalloproteinases and histone deacetylase in oxidative stress-induced degradation of the endothelial glycocalyx.
        Am J Physiol Heart Circ Physiol. 2019; 316: H647-H663
        • Adamson R.H.
        • Clark J.F.
        • Radeva M.
        • Kheirolomoom A.
        • Ferrara K.W.
        • Curry F.E.
        Albumin modulates S1P delivery from red blood cells in perfused microvessels: mechanism of the protein effect.
        Am J Physiol Heart Circ Physiol. 2014; 306: H1011-H1017
        • Xiong Y.
        • Hla T.
        S1P control of endothelial integrity.
        Curr Top Microbiol Immunol. 2014; 378: 85-105
        • Ksiazek M.
        • Chacinska M.
        • Chabowski A.
        • Baranowski M.
        Sources, metabolism, and regulation of circulating sphingosine-1-phosphate.
        J Lipid Res. 2015; 56: 1271-1281
        • Aldecoa C.
        • Llau J.V.
        • Nuvials X.
        • Artigas A.
        Role of albumin in the preservation of endothelial glycocalyx integrity and the microcirculation: a review.
        Ann Intensive Care. 2020; 10: 85
        • Vincent J.L.
        • Russell J.A.
        • Jacob M.
        • et al.
        Albumin administration in the acutely ill: what is new and where next?.
        Crit Care. 2014; 18: 231
        • Wang G.
        • Zhang H.
        • Liu D.
        • Wang X.
        Resuscitation fluids as drugs: targeting the endothelial glycocalyx.
        Chin Med J (Engl). 2022; 135: 137-144
        • Wu F.
        • Chipman A.
        • Pati S.
        • Miyasawa B.
        • Corash L.
        • Kozar R.A.
        Resuscitative strategies to modulate the endotheliopathy of trauma: from cell to patient.
        Shock. 2020; 53: 575-584
        • Ferrer R.
        • Mateu X.
        • Maseda E.
        • Yebenes J.C.
        • Aldecoa C.
        • De Haro C.
        • et al.
        Non-oncotic properties of albumin. A multidisciplinary vision about the implications for critically ill patients.
        Expert Rev Clin Pharmacol. 2018; 11: 125-137
        • Alves N.G.
        • Trujillo A.N.
        • Breslin J.W.
        • Yuan S.Y.
        Sphingosine 1-phosphate reduces hemorrhagic shock and resuscitation-induced microvascular leakage by protecting endothelial mitochondrial integrity.
        Shock. 2019; 52: 423-433
        • Raoufinia R.
        • Mota A.
        • Keyhanvar N.
        • Safari F.
        • Shamekhi S.
        • Abdolalizadeh J.
        Overview of albumin and its purification methods.
        Adv Pharm Bull. 2016; 6: 495-507
        • Yand Q.
        • Wijerathne H.
        • Langston J.C.
        • Kiani M.F.
        • Kilpatrick L.E.
        Emerging approaches to understanding microvascular endothelial heterogeneity: a roadmap for developing anti-inflammatory therapeutics.
        Int J Mol Sci. 2021; 22: 7770
        • Jambusaria A.
        • Hong Z.
        • Zhang L.
        • et al.
        Endothelial hetro geneity across distant vascular beds during homeostasis and inflammation.
        eLife. 2020; 9
        • Zeng Y.
        • Adamson R.H.
        • Curry F.R.
        • Tarbell J.M.
        Sphingosine 1-phosphate protects endothelial glycocalyx by inhibiting syndecan-1 shedding.
        Am J Physiol Heart Circ Physiol. 2014; 306: H363-H372
        • Drost C.C.
        • Rovas A.
        • Kusche-Vihrog K.
        • et al.
        Tie2 activation promotes protection and reconstitution of the endothelial glycocalyx in human sepsis.
        Thromb Haemost. 2019; 119: 1827-1838
        • Lukasz A.
        • Hillgruber C.
        • Oberleithner H.
        • et al.
        Endothleila glycocalyx breakdown is mediated by angiopoietin 2.
        Cardiovasc Res. 2017; 113: 671-680
        • Roche M.
        • Rondeau P.
        • Singh N.R.
        • Tarnus E.
        • Bourdon E.
        The antioxidant properties of serum albumin.
        FEBS Lett. 2008; 582: 1783-1787
        • Raza Z.
        • Saleem U.
        • Naureen Z.
        Sphingosine 1-phosphate signaling in ischemia and reperfusion injury.
        Prostaglandins Other Lipid Mediat. 2020; 149: 106436
        • Selim S.
        • Sunkara M.
        • Salous A.K.
        • et al.
        Plasma levels of sphingosine 1-phosphate are strongly correlated with haematocrit, but variably restored by red blood cell transfusions.
        Clin Sci (Lond). 2011; 121: 565-572
        • Plantier J.L.
        • Duretz V.
        • Devos V.
        • Urbain R.
        • Jorieux S.
        Comparison of antioxidant properties of different therapeutic albumin preparations.
        Biologicals. 2016; 44: 226-233
        • Aldecoa C.
        • Liau J.V.
        • Nuvials X.
        • Artigas A.
        Role of albumin in the preservation of endothelial glycocalyx integrity and the microcirculation: a review.
        Ann Intensive Care. 2020; 10
        • Rodrigues S.F.
        • Granger D.N.
        Blood cells and endothelial barrier function.
        Tissue Barriers. 2015; 3e978720
        • Zeng Y.
        • Liu X.H.
        • Tarbell J.
        • Fu B.
        Sphingosine 1-phosphate induced synthesis of glycocalyx on endothelial cells.
        Exp Cell Res. 2015; 339: 90-95
        • Belinskaia D.A.
        • Voronina P.A.
        • Shmurak V.I.
        • Jenkins R.O.
        • Goncharov N.V.
        Serum albumin in health and disease: esterase, antioxidant, transporting and signaling properties.
        Int J Mol Sci. 2021; 22: 10318
        • Ziegler A.C.
        • Graler M.H.
        Barrier maintenance by S1P during inflammation and sepsis.
        Tissue Barriers. 2021; 9: 1940069