Regulatory mechanisms, prophylaxis and treatment of vascular leakage following severe trauma and shock

Chen-Yang Duan; Jie Zhang; Hui-Ling Wu; Tao Li; Liang-Ming Liu

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Regulatory mechanisms, prophylaxis and treatment of vascular leakage following severe trauma and shock

REVIEW | Updated：2026-03-12

- Regulatory mechanisms, prophylaxis and treatment of vascular leakage following severe trauma and shock
- Regulatory mechanisms, prophylaxis and treatment of vascular leakage following severe trauma and shock
- MMR 2017年4卷第2期页码：109-120
- Affiliations：
  
  State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China
- Author bio：
  
  *: lt200132@163.com;
  liangmingliu@yahoo.com
- Funds：
  
  the National Natural Science Foundation of China(81570441);the Program for Changjiang Scholars and the Innovative Research Team in the University(IRT1216)
- DOI：
  中图分类号：
- 纸质出版：2017-06
- Accepted：
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Regulatory mechanisms, prophylaxis and treatment of vascular leakage following severe trauma and shock[J]. MMR, 2017,4(2):109-120.

Chen-Yang Duan, Jie Zhang, Hui-Ling Wu, et al. Regulatory mechanisms, prophylaxis and treatment of vascular leakage following severe trauma and shock[J]. Military Medical Research, 2017, 4(2): 109-120.
Regulatory mechanisms, prophylaxis and treatment of vascular leakage following severe trauma and shock[J]. MMR, 2017,4(2):109-120. DOI：

Chen-Yang Duan, Jie Zhang, Hui-Ling Wu, et al. Regulatory mechanisms, prophylaxis and treatment of vascular leakage following severe trauma and shock[J]. Military Medical Research, 2017, 4(2): 109-120. DOI：

摘要

Abstract

Vascular leakage

or increased vascular permeability

is a common but important pathological process for various critical diseases

including severe trauma

shock

sepsis

and multiple organ dysfunction syndrome (MODS)

and has become one of the most important causes of death for intensive care units (ICU) patients. Currently

although there has been some progress in knowledge of the pathogenesis of these vascular disorders

the detailed mechanisms remain unclear

and effective prophylaxis and treatment are still lacking. In this study

we aimed to provide a review of the literature regarding the regulatory mechanisms and prophylaxis as well as the treatment of vascular leakage in critical diseases such as severe trauma and shock

which could be beneficial for the overall clinical treatment of vascular leakage disorders.

关键词

Keywords

references

Lee YS , Kim SY , Kwon CW , Song HG , Lee YK , Kim HJ , et al . Two cases of systemic capillary leak syndrome that were treated with pentastarch . Korean J Intern Med . 2007 ; 22 : 130 - 2 .

Munoz-Guillen NM , Leon-Lopez R , de la Cal-Ramirez MA , Duenas-Jurado JM . Systemic capillary leak syndrome: hypoalbuminemia, hemoconcentration and shock. Presentation of a case . Semergen . 2014 ; 40 : e33 - 6 .

Dhir V , Arya V , Malav IC , Suryanarayanan BS , Gupta R , Dey AB . Idiopathic systemic capillary leak syndrome (scls): case report and systematic review of cases reported in the last 16 years . Intern Med . 2007 ; 46 : 899 - 904 .

Rabbolini DJ , Ange N , Walters GD , Pidcock M , Randall KL . Systemic capillary leak syndrome: recognition prevents morbidity and mortality . Intern Med J . 2013 ; 43 : 1145 - 7 .

Gousseff M , Amoura Z . [Idiopathic capillary leak syndrome] . Rev Med Interne . 2009 ; 30 : 754 - 68 .

Chihara R , Nakamoto H , Arima H , Moriwaki K , Kanno Y , Sugahara S , et al . Systemic capillary leak syndrome . Intern Med . 2002 ; 41 : 953 - 6 .

Lucas CE , Ledgerwood AM . FFP: RBC resuscitation ratio and post-shock fluid uptake . JAMA Surg . 2013 ; 3 : 239 - 44 .

Mehta D , Malik AB . Signaling mechanisms regulating endothelial permeability . Physiol Rev . 2006 ; 86 : 279 - 367 .

Tsukita S , Furuse M . Pores in the wall: claudins constitute tight junction strands containing aqueous pores . J Cell Biol . 2000 ; 149 : 13 - 6 .

Vestweber D . VE-cadherin: the major endothelial adhesion molecule controlling cellular junctions and blood vessel formation . Arterioscler Thromb Vasc Biol . 2008 ; 28 : 223 - 32 .

Sukriti S , Tauseef M , Yazbeck P , Mehta D . Mechanisms regulating endothelial permeability . Pulm Circ . 2014 ; 4 : 535 - 51 .

Orlova VV , Economopoulou M , Lupu F , Santoso S , Chavakis T . Junctional adhesion molecule-c regulates vascular endothelial permeability by modulating ve-cadherin-mediated cell-cell contacts . J Exp Med . 2006 ; 203 : 2703 - 14 .

Wong V . Phosphorylation of occludin correlates with occludin localization and function at the tight junction . Am J Physiol . 1997 ; 273 : C1859 - 67 .

Van Itallie CM , Tietgens AJ , Logrande K , Aponte A , Gucek M , Anderson JM . Phosphorylation of claudin-2 on serine 208 promotes membrane retention and reduces trafficking to lysosomes . J Cell Sci . 2012 ; 125 : 4902 - 12 .

Blasig IE , Bellmann C , Cording J , Del Vecchio G , Zwanziger D , Huber O , et al . Occludin protein family: oxidative stress and reducing conditions . Antioxid Redox Signal . 2011 ; 15 : 1195 - 219 .

Krause G , Winkler L , Mueller SL , Haseloff RF , Piontek J , Blasig IE . Structure and function of claudins . Biochim Biophys Acta . 2008 ; 1778 : 631 - 45 .

Bazzoni G . Pathobiology of junctional adhesion molecules . Antioxid Redox Signal . 2011 ; 15 : 1221 - 34 .

Gonzalez JE , Digeronimo RJ , Arthur DE , King JM . Remodeling of the tight junction during recovery from exposure to hydrogen peroxide in kidney epithelial cells . Free Radic Biol Med . 2009 ; 47 : 1561 - 9 .

Hashimoto Y , Tada M , Iida M , Nagase S , Hata T , Watari A , et al . Generation and characterization of a human-mouse chimeric antibody against the extracellular domain of claudin-1 for cancer therapy using a mouse model . Biochem Biophys Res Commun . 2016 ; 477 : 91 - 5 .

Gonzalez-Mariscal L , Quiros M , Diaz-Coranguez M . Zo proteins and redoxdependent processes . Antioxid Redox Signal . 2011 ; 15 : 1235 - 53 .

Chen J , Chen G , Li J , Qian C , Mo H , Gu C , et al . Melatonin attenuates inflammatory response-induced brain edema in early brain injury following a subarachnoid hemorrhage: a possible role for the regulation of proinflammatory cytokines . J Pineal Res . 2014 ; 57 : 340 - 7 .

Oakley R , Tharakan B . Vascular hyperpermeability and aging . Aging Dis . 2014 ; 5 : 114 - 25 .

Schulte D , Kuppers V , Dartsch N , Broermann A , Li H , Zarbock A , et al . Stabilizing the ve-cadherin- catenin complex blocks leukocyte extravasation and vascular permeability . EMBO J . 2011 ; 30 : 4157 - 70 .

Vestweber D , Winderlich M , Cagna G , Nottebaum AF . Cell adhesion dynamics at endothelial junctions: VE-cadherin as a major player . Trends Cell Biol . 2009 ; 19 : 8 - 15 .

Dejana E . Endothelial cell-cell junctions: happy together . Nat Rev Mol Cell Biol . 2004 ; 5 : 261 - 70 .

Ruffer C , Strey A , Janning A , Kim KS , Gerke V . Cell-cell junctions of dermal microvascular endothelial cells contain tight and adherens junction proteins in spatial proximity . Biochemistry . 2004 ; 43 : 5360 - 9 .

Titchenell PM , Lin CM , Keil JM , Sundstrom JM , Smith CD , Antonetti DA . Novel atypical pkc inhibitors prevent vascular endothelial growth factorinduced blood-retinal barrier dysfunction . Biochem J. 2012 ; 446 : 455 - 67 .

Yu Y , Lv N , Lu Z , Zheng YY , Zhang WC , Chen C , et al . Deletion of myosin light chain kinase in endothelial cells has a minor effect on the lipopolysaccharide-induced increase in microvascular endothelium permeability in mice . FEBS J . 2012 ; 279 : 1485 - 94 .

Birukova AA , Zebda N , Fu P , Poroyko V , Cokic I , Birukov KG . Association between adherens junctions and tight junctions via rap1 promotes barrier protective effects of oxidized phospholipids . J Cell Physiol . 2011 ; 226 : 2052 - 62 .

Maiers JL , Peng X , Fanning AS , Demali KA . Zo-1 recruitment to alphacatenin—a novel mechanism for coupling the assembly of tight junctions to adherens junctions . J Cell Sci . 2013 ; 126 : 3904 - 15 .

Feng D , Nagy JA , Pyne K , Hammel I , Dvorak HF , Dvorak AM . Pathways of macromolecular extravasation across microvascular endothelium in response to vpf/vegf and other vasoactive mediators . Microcirculation . 1999 ; 6 : 23 - 44 .

Feng Y , Venema VJ , Venema RC , Tsai N , Behzadian MA , Caldwell RB . Vegfinduced permeability increase is mediated by caveolae . Invest Ophthalmol Vis Sci . 1999 ; 40 : 157 - 67 .

Feng D , Nagy JA , Hipp J , Dvorak HF , Dvorak AM . Vesiculo-vacuolar organelles and the regulation of venule permeability to macromolecules by vascular permeability factor, histamine, and serotonin . J Exp Med . 1996 ; 183 : 1981 - 6 .

Hayashi Y , Edwards NA , Proescholdt MA , Oldfield EH , Merrill MJ . Regulation and function of aquaporin-1 in glioma cells . Neoplasia . 2007 ; 9 : 777 - 87 .

Egan JR , Butler TL , Cole AD , Aharonyan A , Baines D , Street N , et al . Myocardial ischemia is more important than the effects of cardiopulmonary bypass on myocardial water handling and postoperative dysfunction: a pediatric animal model . J Thorac Cardiovasc Surg . 2008 ; 136 : 1265 - 73 .

Yakata K , Hiroaki Y , Ishibashi K , Sohara E , Sasaki S , Mitsuoka K , et al . Aquaporin-11 containing a divergent npa motif has normal water channel activity . Biochim Biophys Acta . 2007 ; 1768 : 688 - 93 .

Drobná Z , Walton FS , Paul DS , Xing W , Thomas DJ , Styblo M . Metabolism of arsenic in human liver: the role of membrane transporters . Arch Toxicol . 2010 ; 84 : 3 - 16 .

Teng WY , Gao Y , Tian L , Liu HL , Ge YS , Zhang CD . The relationship between aquaporin-4 mrna expression and blood-brain barrier permeability after experimental cerebral hemorrhage in rats . Chin J Arterioseler . 2006 ; 14 : 3 .

Ke C , Poon WS , Ng HK , Pang JC , Chan Y . Heterogeneous responses of aquaporin-4 in oedema formation in a replicated severe traumatic brain injury model in rats . Neurosci Lett . 2001 ; 301 : 21 - 4 .

Liu H , Yang M , Qiu GP , Zhuo F , Yu WH , Sun SQ , Xiu Y . Aquaporin 9 in rat brain after severe traumatic brain injury . Arq Neuropsiquiatr . 2012 ; 70 : 214 - 20 .

Razani B , Woodman SE , Lisanti MP . Caveolae: from cell biology to animal physiology . Pharmacol Rev . 2002 ; 54 : 431 - 67 .

Zhang YZ , Jin S . The advances in endothelial caveolae and its proteins caveolins and cavins . J Med Sci Cent South China . 2012 ; 40 : 9 .

Couet J , Belanger MM , Roussel E , Drolet MC . Cell biology of caveolae and caveolin . Adv Drug Deliv Rev . 2001 ; 49 : 223 - 35 .

Scherer PE , Lewis RY , Volonte D , Engelman JA , Galbiati F , Couet J , et al . Cell-type and tissue-specific expression of caveolin-2. Caveolins 1 and 2 co-localize and form a stable hetero-oligomeric complex in vivo . J Biol Chem . 1997 ; 272 : 29337 - 46 .

Wisse E , Jacobs F , Topal B , Frederik P , De Geest B . The size of endothelial fenestrae in human liver sinusoids: implications for hepatocyte-directed gene transfer . Gene Ther . 2008 ; 15 : 1193 - 9 .

Xu C , Chang A , Hack BK , Eadon MT , Alper SL , Cunningham PN . Tnfmediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis . Kidney Int . 2014 ; 85 : 72 - 81 .

Ryan GB , Karnovsky MJ . Distribution of endogenous albumin in the rat glomerulus: role of hemodynamic factors in glomerular barrier function . Kidney Int . 1976 ; 9 : 36 - 45 .

Hjalmarsson C , Lidell ME , Haraldsson B . Beneficial effects of orosomucoid on the glomerular barrier in puromycin aminonucleoside-induced nephrosis . Nephrol Dial Transplant . 2006 ; 21 : 1223 - 30 .

Dudzinski DM , Igarashi J , Greif D , Michel T . The regulation and pharmacology of endothelial nitric oxide synthase . Annu Rev Pharmacol Toxicol . 2006 ; 46 : 235 - 76 .

Braet F , Riches J , Geerts W , Jahn KA , Wisse E , Frederik P . Three-dimensional organization of fenestrae labyrinths in liver sinusoidal endothelial cells . Liver Int . 2009 ; 29 : 603 - 13 .

De Bock M , Culot M , Wang N , da Costa A , Decrock E , Bol M , et al . Low extracellular Ca2+ conditions induce an increase in brain endothelial permeability that involves intercellular Ca2+ waves . Brain Res . 2012 ; 1487 : 78 - 87 .

Yuan Y , Huang Q , Wu HM . Myosin light chain phosphorylation: Modulation of basal and agonist-stimulated venular permeability . Am J Physiol . 1997 ; 272 : H1437 - 43 .

Leung DW , Cachianes G , Kuang WJ , Goeddel DV , Ferrara N . Vascular endothelial growth factor is a secreted angiogenic mitogen . Science . 1989 ; 246 : 1306 - 9 .

Potter MD , Barbero S , Cheresh DA . Tyrosine phosphorylation of ve-cadherin prevents binding of p120- and beta-catenin and maintains the cellular mesenchymal state . J Biol Chem . 2005 ; 280 : 31906 - 12 .

Bates DO , Hillman NJ , Williams B , Neal CR , Pocock TM . Regulation of microvascular permeability by vascular endothelial growth factors . J Anat . 2002 ; 200 : 581 - 97 .

Hendel A , Hsu I , Granville DJ . Granzyme b releases vascular endothelial growth factor from extracellular matrix and induces vascular permeability . Lab Invest . 2014 ; 94 : 716 - 25 .

Suarez S , Ballmer-Hofer K . Vegf transiently disrupts gap junctional communication in endothelial cells . J Cell Sci . 2001 ; 114 : 1229 - 35 .

Chen J , Braet F , Brodsky S , Weinstein T , Romanov V , Noiri E , et al . Vegfinduced mobilization of caveolae and increase in permeability of endothelial cells . Am J Physiol Cell Physiol . 2002 ; 282 : C1053 - 63 .

Esser S , Wolburg K , Wolburg H , Breier G , Kurzchalia T , Risau W . Vascular endothelial growth factor induces endothelial fenestrations in vitro . J Cell Biol . 1998 ; 140 : 947 - 59 .

Breslin JW , Pappas PJ , Cerveira JJ , Hobson 2nd RW , Durán WN . VEGF increases endothelial permeability by separate signaling pathways involving ERK-1/2 and nitric oxide . Am J Physiol Heart Circ Physiol . 2003 ; 284 : H92 - H100 .

Marin N , Zamorano P , Carrasco R , Mujica P , Gonzalez FG , Quezada C , et al . S-nitrosation of beta-catenin and p120 catenin: a novel regulatory mechanism in endothelial hyperpermeability . Circ Res . 2012 ; 111 : 553 - 63 .

Thibeault S , Rautureau Y , Oubaha M , Faubert D , Wilkes BC , Delisle C , et al . Snitrosylation of beta-catenin by enos-derived no promotes vegf-induced endothelial cell permeability . Mol Cell . 2010 ; 39 : 468 - 76 .

Wiggins-Dohlvik K , Merriman M , Shaji CA , Alluri H , Grimsley M , Davis ML , et al . Tumor necrosis factor-α disruption of brain endothelial cell barrier is mediated through matrix metalloproteinase-9 . Am J Surg . 2014 ; 208 : 954 - 60 .

Hargett LA , Bauer NN . On the origin of microparticles: trom “Platelet dust” to mediators of intercellular communication . Pulm Circ . 2013 ; 3 : 329 - 40 .

Angelillo-Scherrer A . Leukocyte-derived microparticles in vascular homeostasis . Circ Res . 2012 ; 110 : 356 - 69 .

Burger D , Montezano AC , Nishigaki N , He Y , Carter A , Touyz RM . Endothelial microparticle formation by angiotensin ii is mediated via ang ii receptor type i/nadph oxidase/ rho kinase pathways targeted to lipid rafts . Arterioscler Thromb Vasc Biol . 2011 ; 31 : 1898 - 907 .

Gamble JR , Drew J , Trezise L , Underwood A , Parsons M , Kasminkas L , et al . Angiopoietin-1 is an antipermeability and anti- inflammatory agent in vitro and targets cell junctions . Circ Res . 2000 ; 87 : 603 - 7 .

Thurston G , Rudge JS , Ioffe E , Zhou H , Ross L , Croll SD , et al . Angiopoietin-1 protects the adult vasculature against plasma leakage . Nat Med . 2000 ; 6 : 460 - 3 .

Fujikawa K , de Aos SI , Jain SK , Presman E , Christensen RA , Varticovski L . Role of pi 3-kinase in angiopoietin-1-mediated migration and attachmentdependent survival of endothelial cells . Exp Cell Res . 1999 ; 253 : 663 - 72 .

Gardner AW , Parker DE , Montgomery PS , Sosnowska D , Casanegra AI , Esponda OL , et al . Impaired vascular endothelial growth factor a and inflammation in patients with peripheral artery disease . Angiology . 2014 ; 65 : 683 - 90 .

Zan L , Zhang X , Xi Y , Wu H , Song Y , Teng G , et al . Src regulates angiogenic factors and vascular permeability after focal cerebral ischemia- reperfusion . Neuroscience . 2014 ; 262 : 118 - 28 .

Cui H , Okamoto Y , Yoshioka K , Du W , Takuwa N , Zhang W , et al . Sphingosine-1-phosphate receptor 2 protects against anaphylactic shock through suppression of endothelial nitric oxide synthase in mice . J Allergy Clin Immunol . 2013 ; 132 : 1205–14. e9 .

Choi YH , Jin GY , Li LC , Yan GH . Inhibition of protein kinase c delta attenuates allergic airway inflammation through suppression of pi3k/akt/mtor/hif-1 alpha/vegf pathway . Plos One . 2013 ; 8 : e81773 .

Monti M , Solito R , Puccetti L , Pasotti L , Roggeri R , Monzani E , et al . Protective effects of novel metal-nonoates on the cellular components of the vascular system . J Pharmacol Exp Ther . 2014 ; 351 : 500 - 9 .

Silva BR , Lunardi CN , Araki K , Biazzotto JC , Da Silva RS , Bendhack LM . Gold nanoparticle modifies nitric oxide release and vasodilation in rat aorta . J Chem Biol . 2014 ; 7 : 57 - 65 .

Tian X , Tian Y , Gawlak G , Sarich N , Wu T , Birukova AA . Control of vascular permeability by atrial natriuretic peptide via a gef-h1-dependent mechanism . J Biol Chem . 2014 ; 289 : 5168 - 83 .

Ichiki T , Izumi R , Cataliotti A , Larsen AM , Sandberg SM , Burnett Jr JC . Endothelial permeability in vitro and in vivo: protective actions of anp and omapatrilat in experimental atherosclerosis . Peptides . 2013 ; 48 : 21 - 6 .

Chen W , Oberwinkler H , Werner F , Gaßner B , Nakagawa H , Feil R , et al . Atrial natriuretic peptide-mediated inhibition of microcirculatory endothelial Ca 2+ and permeability response to histamine involves cGMP-dependent protein kinase I and TRPC6 channels . Arterioscler Thromb Vasc Biol . 2013 ; 33 : 2121 - 9 .

Maharjan S , Kim K , Agrawal V , Choi HJ , Kim NJ , Kim YM , et al . Sac-1004, a novel vascular leakage blocker, enhances endothelial barrier through the camp/rac/cortactin pathway . Biochem Biophys Res Commun . 2013 ; 435 : 420 - 7 .

Kannan L , Kis-Toth K , Yoshiya K , Thai TH , Sehrawat S , Mayadas TN , et al . Rspondin3 prevents mesenteric ischemia/reperfusion- induced tissue damage by tightening endothelium and preventing vascular leakage . Proc Natl Acad Sci U S A . 2013 ; 110 : 14348 - 53 .

Zhou N , Xu T , Bai Y , Prativa S , Xu JZ , Li K , et al . Protective effects of urinary trypsin inhibitor on vascular permeability following subarachnoid hemorrhage in a rat model . CNS Neurosci Ther . 2013 ; 19 : 659 - 66 .

Tong N , Zhang Z , Zhang W , Qiu Y , Gong Y , Yin L , et al . Diosmin alleviates retinal edema by protecting the blood-retinal barrier and reducing retinal vascular permeability during ischemia/reperfusion injury . Plos One . 2013 ; 8 : e61794 .

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