Emerging therapeutic strategies to prevent infection-related microvascular endothelial activation and dysfunction

被引:51
作者
Darwish, Ilyse [1 ]
Liles, W. Conrad [1 ,2 ,3 ]
机构
[1] Toronto Gen Hosp, Univ Hlth Network, Sandra Rotman Ctr Global Hlth, Sandra A Rotman Labs, Toronto, ON, Canada
[2] Univ Toronto, Div Infect Dis, Dept Med, Toronto, ON, Canada
[3] Univ Washington, Dept Med, Seattle, WA USA
基金
加拿大健康研究院;
关键词
endothelium; microvascular leak; emerging therapeutics; infectious diseases; sepsis; acute lung injury; MESENCHYMAL STEM-CELLS; ATRIAL-NATRIURETIC-PEPTIDE; EXCESS CIRCULATING ANGIOPOIETIN-2; MULTIPLE ORGAN DYSFUNCTION; INDUCED ACUTE LUNG; SPHINGOSINE; 1-PHOSPHATE; GROWTH-FACTOR; VASCULAR LEAK; SEPTIC SHOCK; PROTEIN-C;
D O I
10.4161/viru.25740
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Recent evidence suggests that loss of endothelial barrier function and resulting microvascular leak play important mechanistic roles in the pathogenesis of infection-related end-organ dysfunction and failure. Several distinct therapeutic strategies, designed to prevent or limit infection-related microvascular endothelial activation and permeability, thereby mitigating end-organ injury/dysfunction, have recently been investigated in pre-clinical models. In this review, these potential therapeutic strategies, namely, VEGFR2/Src antagonists, sphingosine-1-phosphate agonists, fibrinopeptide B15-42, slit2N, secinH3, angiopoietin-1/tie-2 agonists, angiopoietin-2 antagonists, statins, atrial natriuretic peptide, and mesenchymal stromal (stem) cells, are discussed in terms of their translational potential for the management of clinical infectious diseases.
引用
收藏
页码:572 / 582
页数:11
相关论文
共 113 条
[1]   Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death [J].
Abraham, E ;
Laterre, P ;
Garg, R ;
Levy, H ;
Talwar, D ;
Trzaskoma, BL ;
Francois, B ;
Guy, JS ;
Bruckmann, M ;
Rea-Neto, A ;
Rossaint, R ;
Perrotin, D ;
Sablotzki, A ;
Arkins, N ;
Utterback, BG ;
Macias, WL .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (13) :1332-1341
[2]   Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis [J].
Alfieri, Alessio ;
Watson, Jay J. ;
Kammerer, Richard A. ;
Tasab, Mohammed ;
Progias, Pavlos ;
Reeves, Kimberly ;
Brown, Nicola J. ;
Brookes, Zoe L. .
CRITICAL CARE, 2012, 16 (05)
[3]   N-terminal Slit2 inhibits HIV-1 replication by regulating the actin cytoskeleton [J].
Anand, Appakkudal R. ;
Zhao, Helong ;
Nagaraja, Tirumuru ;
Robinson, Lisa A. ;
Ganju, Ramesh K. .
RETROVIROLOGY, 2013, 10
[4]   Endothelial cell VE-cadherin functions as a receptor for the β15-42 sequence of fibrin [J].
Bach, TL ;
Barsigian, C ;
Yaen, CH ;
Martinez, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (46) :30719-30728
[5]   ATRIOPEPTIN INHIBITION OF THROMBIN-MEDIATED CHANGES IN THE MORPHOLOGY AND PERMEABILITY OF ENDOTHELIAL MONOLAYERS [J].
BARON, DA ;
LOFTON, CE ;
NEWMAN, WH ;
CURRIE, MG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (09) :3394-3398
[6]   Syndecan-1 couples the insulin-like growth factor-1 receptor to inside-out integrin activation [J].
Beauvais, DeannaLee M. ;
Rapraeger, Alan C. .
JOURNAL OF CELL SCIENCE, 2010, 123 (21) :3796-3807
[7]   Syndecan-1 regulates αvβ3 and αvβ5 integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor [J].
Beauvais, DeannaLee M. ;
Ell, Brian J. ;
McWhorter, Andrea R. ;
Rapraeger, Alan C. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (03) :691-705
[8]   Efficacy and safety of recombinant human activated protein C for severe sepsis. [J].
Bernard, GR ;
Vincent, JL ;
Laterre, P ;
LaRosa, SP ;
Dhainaut, JF ;
Lopez-Rodriguez, A ;
Steingrub, JS ;
Garber, GE ;
Helterbrand, JD ;
Ely, EW ;
Fisher, CJ .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (10) :699-709
[9]   Marrow stromal stem cells [J].
Bianco, P ;
Robey, PG .
JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (12) :1663-1668
[10]   Relation of markers of inflammation (C-reactive protein, fibrinogen, von Willebrand factor, and leukocyte count) and statin therapy to long-term mortality in patients with angiographically proven coronary artery disease [J].
Bickel, C ;
Rupprecht, HJ ;
Blankenberg, S ;
Espiniola-Klein, C ;
Schlitt, A ;
Rippin, G ;
Hafner, G ;
Treude, R ;
Othman, H ;
Hofmann, KP ;
Meyer, J .
AMERICAN JOURNAL OF CARDIOLOGY, 2002, 89 (08) :901-908