Endothelial dysfunction is a potential contributor to multiple organ failure and mortality in aged mice subjected to septic shock: Preclinical studies in a murine model of cecal ligation and puncture

Critical Care

Volumn 18, Issue 5, 2014, Pages 1-15

  Coletta, Ciro ^a   Módis, Katalin ^a,c   Oláh, Gábor ^a   Brunyánszki, Attila ^a   Herzig, Daniela S ^a   Sherwood, Edward R ^a,d   Ungvári, Zoltán ^b   Szabo, Csaba ^a  

^a University of Texas Medical Branch School of Medicine   (United States)

^b UNIVERSITY OF OKLAHOMA COLLEGE OF MEDICINE   (United States)

^c LAKEHEAD UNIVERSITY   (Canada)

^d VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENDOTHELIAL NITRIC OXIDE SYNTHASE;

AGING; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL DAMAGE; CELL FUNCTION; CELL INFILTRATION; CONTROLLED STUDY; DISEASE SEVERITY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; ENDOTHELIAL DYSFUNCTION; EX VIVO STUDY; ISOLATED LIVER; LIVER MITOCHONDRION; MALE; MONONUCLEAR CELL; MORTALITY; MOUSE; MULTIPLE ORGAN FAILURE; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PROGNOSIS; SEPTIC SHOCK; SURVIVAL RATE; THORACIC AORTA; VASCULAR RING; ADVERSE EFFECTS; ANIMAL; C57BL MOUSE; CECUM; DISEASE MODEL; LIGATION; METABOLISM; ORGAN CULTURE TECHNIQUE; PATHOPHYSIOLOGY; PHYSIOLOGY; PUNCTURE; TRANSGENIC MOUSE; TRENDS; VASCULAR ENDOTHELIUM;

AGING; ANIMALS; CECUM; DISEASE MODELS, ANIMAL; ENDOTHELIUM, VASCULAR; LIGATION; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MORTALITY; MULTIPLE ORGAN FAILURE; ORGAN CULTURE TECHNIQUES; OXIDATIVE STRESS; PUNCTURES; SHOCK, SEPTIC;

EID: 84908099568     PISSN: 13648535     EISSN: 1466609X     Source Type: Journal    
DOI: 10.1186/s13054-014-0511-3     Document Type: Article

References (69)

1. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2001, 348:1546-1554. 10.1056/NEJMoa022139.
2. Martin GS, Mannino DM, Moss M. The effect of age on the development and outcome of adult sepsis. Crit Care Med 2006, 34:15-21. 10.1097/01.CCM.0000194535.82812.BA, 16374151.
3. Altura BM, Gebrewold A, Burton RW. Failure of microscopic metarterioles to elicit vasodilator responses to acetylcholine, bradykinin, histamine and substance P after ischemic shock, endotoxemia and trauma: possible role of endothelial cells. Microcirc Endothelium Lymphatics 1985, 2:121-127. 2425237.
4. Szabo C, Farago M, Horvath I, Lohinai Z, Kovach AG. Hemorrhagic hypotension impairs endothelium-dependent relaxations in the renal artery of the cat. Circ Shock 1992, 36:238-241. 1611708.
5. Wang P, Ba ZF, Chaudry IH. Endothelial cell dysfunction occurs after hemorrhage in nonheparinized but not in preheparinized models. J Surg Res 1993, 54:499-506. 10.1006/jsre.1993.1077, 8361175.
6. Parker JL, Adams HR. Selective inhibition of endothelium-dependent vasodilator capacity by Escherichia coli endotoxemia. Circ Res 1993, 72:539-551. 10.1161/01.RES.72.3.539, 7679334.
7. Szabo C, Cuzzocrea S, Zingarelli B, O'Connor M, Salzman AL. Endothelial dysfunction in a rat model of endotoxic shock. Importance of the activation of poly (ADP-ribose) synthetase by peroxynitrite. J Clin Invest 1997, 100:723-735. 10.1172/JCI119585, 9239421.
8. Szabo C. Alterations in nitric oxide production in various forms of circulatory shock. New Horiz 1995, 3:2-32. 7535648.
9. Vallet B. Bench-to-bedside review: endothelial cell dysfunction in severe sepsis: a role in organ dysfunction?. Crit Care 2003, 7:130-138. 10.1186/cc1864, 12720559.
10. Kubli S, Boëgli Y, Ave AD, Liaudet L, Revelly JP, Golay S, Broccard A, Waeber B, Schaller MD, Feihl F. Endothelium-dependent vasodilation in the skin microcirculation of patients with septic shock. Shock 2003, 19:274-280. 10.1097/00024382-200303000-00013, 12630529.
11. Kienbaum P, Prante C, Lehmann N, Sander A, Jalowy A, Peters J. Alterations in forearm vascular reactivity in patients with septic shock. Anaesthesia 2008, 63:121-128. 10.1111/j.1365-2044.2007.05286.x, 18211441.
12. Davis JS, Yeo TW, Thomas JH, McMillan M, Darcy CJ, McNeil YR, Cheng AC, Celermajer DS, Stephens DP, Anstey NM. Sepsis-associated microvascular dysfunction measured by peripheral arterial tonometry: an observational study. Crit Care 2009, 13:R155. 10.1186/cc8055, 19778457.
13. Hein OV, Misterek K, Tessmann JP, van Dossow V, Krimphove M, Spies C. Time course of endothelial damage in septic shock: prediction of outcome. Crit Care 2005, 9:R323-R330. 10.1186/cc3532, 16137344.
14. Duffy MJ, Mullan BA, Craig TR, Shyamsundar M, Mac Sweeney RE, Thompson G, Stevenson M, McAuley DF. Impaired endothelium-dependent vasodilatation is a novel predictor of mortality in intensive care. Crit Care Med 2011, 39:629-635. 10.1097/CCM.0b013e318206bc4a, 21242802.
15. Wichterman KA, Baue AE, Chaudry IH. Sepsis and septic shock-a review of laboratory models and a proposal. J Surg Res 1980, 29:189-201. 10.1016/0022-4804(80)90037-2, 6997619.
16. Soriano FG, Lorigados CB, Pacher P, Szabo C. Effects of a potent peroxynitrite decomposition catalyst in murine models of endotoxemia and sepsis. Shock 2011, 35:560-566. 10.1097/SHK.0b013e31820fe5d5, 21263378.
17. Coletta C, Papapetropoulos A, Erdelyi K, Olah G, Módis K, Panopoulos P, Asimakopoulou A, Gerö D, Sharina I, Martin E, Szabo C. Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation. Proc Natl Acad Sci USA 2012, 109:9161-9166. 10.1073/pnas.1202916109, 22570497.
18. Gerö D, Szoleczky P, Suzuki K, Módis K, Oláh G, Coletta C, Szabo C. Cell-based screening identifies paroxetine as an inhibitor of diabetic endothelial dysfunction. Diabetes 2013, 62:953-964. 10.2337/db12-0789, 23223176.
19. Módis K, Coletta C, Erdélyi K, Papapetropoulos A, Szabo C. Intramitochondrial hydrogen sulfide production by 3-mercaptopyruvate sulfurtransferase maintains mitochondrial electron flow and supports cellular bioenergetics. FASEB J 2013, 27:601-611. 10.1096/fj.12-216507, 23104984.
20. Szabo C, Modis K. Pathophysiological roles of peroxynitrite in circulatory shock. Shock 2010, 34:S4-S14. 10.1097/SHK.0b013e3181e7e9ba.
21. Huet O, Dupic L, Harrois A, Duranteau J. Oxidative stress and endothelial dysfunction during sepsis. Front Biosci 2011, 16:1986-1995. 10.2741/3835.
22. Paulus P, Jennewein C, Zacharowski K. Biomarkers of endothelial dysfunction: can they help us deciphering systemic inflammation and sepsis?. Biomarkers 2011, 16:S11-S21. 10.3109/1354750X.2011.587893, 21707440.
23. Szabo C, Goldstein B. Endothelial dysfunction as predictor of mortality in sepsis. Crit Care Med 2011, 39:878-879. 10.1097/CCM.0b013e31820a52ba, 21613831.
24. Buwalda M, Ince C. Opening the microcirculation: can vasodilators be useful in sepsis?. Int Care Med 2002, 28:1208-1217. 10.1007/s00134-002-1407-2.
25. Luiking YC, Poeze M, Dejong CH, Ramsay G, Deutz NE. Sepsis: an arginine deficiency state?. Crit Care Med 2004, 32:2135-2145. 10.1097/01.CCM.0000142939.81045.A0, 15483426.
26. Lamontagne F, Meade M, Ondiveeran HK, Lesur O, Fox-Robichaud AE. Nitric oxide donors in sepsis: a systematic review of clinical and in vivo preclinical data. Shock 2008, 30:653-659. 10.1097/SHK.0b013e3181777eef, 18497711.
27. Jakubowski A. S-nitroso-human-albumin: a new therapeutic approach in endotoxic shock. Pol Arch Med Wewn 2009, 119:501-504. 19776691.
28. Czabanka M, Peter C, Martin E, Walther A. Microcirculatory endothelial dysfunction during endotoxemia-insights into pathophysiology, pathologic mechanisms and clinical relevance. Curr Vasc Pharmacol 2007, 5:266-275. 10.2174/157016107782023389, 17979793.
29. Smith AR, Visioli F, Frei B, Hagen TM. Age-related changes in endothelial nitric oxide synthase phosphorylation and nitric oxide dependent vasodilation: Evidence for a novel mechanism involving sphingomyelinase and ceramide-activated phosphatase 2a. Aging Cell 2006, 5:391-400. 10.1111/j.1474-9726.2006.00232.x, 16930126.
30. Toda N. Age-related changes in endothelial function and blood flow regulation. Pharmacol Ther 2012, 133:159-176. 10.1016/j.pharmthera.2011.10.004, 22079549.
31. Li W, Mital S, Ojaimi C, Csiszar A, Kaley G, Hintze TH. Premature death and age-related cardiac dysfunction in male enos-knockout mice. J Mol Cell Cardiol 2004, 37:671-680. 10.1016/j.yjmcc.2004.05.005, 15350840.
32. Saito H, Sherwood ER, Varma TK, Evers BM. Effects of aging on mortality, hypothermia, and cytokine induction in mice with endotoxemia or sepsis. Mech Ageing Dev 2003, 124:1047-1058. 10.1016/j.mad.2003.08.002, 14659593.
33. Raeven P, Salibasic A, Drechsler S, Weixelbaumer KM, Jafarmadar M, van Griensven M, Bahrami S, Osuchowski MF. A non-lethal traumatic/hemorrhagic insult strongly modulates the compartment-specific PAI-1 response in the subsequent polymicrobial sepsis. PLoS One 2013, 8:e55467. 10.1371/journal.pone.0055467, 23408987.
34. Boengler K, Schulz R, Heusch G. Loss of cardioprotection with ageing. Cardiovasc Res 2009, 83:247-261. 10.1093/cvr/cvp033, 19176601.
35. Lakatta EG, Wang M, Najjar SS. Arterial aging and subclinical arterial disease are fundamentally intertwined at macroscopic and molecular levels. Med Clin North Am 2009, 93:583-604. 10.1016/j.mcna.2009.02.008, 19427493.
36. Herrera MD, Mingorance C, Rodriguez-Rodriguez R, de Sotomayor Alvarez M. Endothelial dysfunction and aging: an update. Ageing Res Rev 2010, 9:142-152. 10.1016/j.arr.2009.07.002, 19619671.
37. Ungvari Z, Buffenstein R, Austad SN, Podlutsky A, Kaley G, Csiszar A. Oxidative stress in vascular senescence: lessons from successfully aging species. Front Biosci 2008, 13:5056-5070. 10.2741/3064, 18508570.
38. Csiszar A, Podlutsky A, Wolin MS, Losonczy G, Pacher P, Ungvari Z. Oxidative stress and accelerated vascular aging: implications for cigarette smoking. Front Biosci 2009, 14:3128-3144. 10.2741/3440.
39. Csiszar A, Pacher P, Kaley G, Ungvari Z. Role of oxidative and nitrosative stress, longevity genes and poly(ADP-ribose) polymerase in cardiovascular dysfunction associated with aging. Curr Vasc Pharmacol 2005, 3:285-291. 10.2174/1570161054368616, 16026324.
40. Rodriguez-Mañas L, El-Assar M, Vallejo S, Lopez-Doriga P, Solis J, Petidier R, Montes M, Nevado J, Castro M, Gomez-Guerrero C, Peiro C, Sanchez-Ferrer CF. Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation. Aging Cell 2009, 8:226-238. 10.1111/j.1474-9726.2009.00466.x, 19245678.
41. Pacher P, Mabley JG, Soriano FG, Liaudet L, Komjati K, Szabo C. Endothelial dysfunction in aging animals: the role of poly(ADP-ribose) polymerase activation. Br J Pharmacol 2002, 135:1347-1350. 10.1038/sj.bjp.0704627, 11906946.
42. Pacher P, Mabley JG, Soriano FG, Liaudet L, Szabo C. Activation of poly(ADP-ribose) polymerase contributes to the endothelial dysfunction associated with hypertension and aging. Int J Mol Med 2002, 9:659-664. 12011985.
43. Pacher P, Vaslin A, Benko R, Mabley JG, Liaudet L, Hasko G, Marton A, Batkai S, Kollai M, Szabo C. A new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging. J Pharmacol Exp Ther 2004, 311:485-491. 10.1124/jpet.104.069658, 15213249.
44. Radovits T, Seres L, Gero D, Berger I, Szabo C, Karck M, Szabo G. Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction. Exp Gerontol 2007, 42:676-685. 10.1016/j.exger.2007.01.013, 17383839.
45. Ungvari Z, Krasnikov BF, Csiszar A, Labinskyy N, Mukhopadhyay P, Pacher P, Cooper AJ, Podlutskaya N, Austad SN, Podlutsky A. Testing hypotheses of aging in long-lived mice of the genus Peromyscus: association between longevity and mitochondrial stress resistance, ROS detoxification pathways, and DNA repair efficiency. Age (Dordr) 2008, 30:121-133. 10.1007/s11357-008-9059-y.
46. Csiszar A, Ungvari Z, Edwards JG, Kaminski P, Wolin MS, Koller A, Kaley G. Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function. Circ Res 2002, 90:1159-1166. 10.1161/01.RES.0000020401.61826.EA, 12065318.
47. Radovits T, Seres L, Gero D, Lin LN, Beller CJ, Chen SH, Zotkina J, Berger I, Groves JT, Szabo C, Szabo G. The peroxynitrite decomposition catalyst FP15 improves ageing-associated cardiac and vascular dysfunction. Mech Ageing Dev 2007, 128:173-181. 10.1016/j.mad.2006.09.005, 17116320.
48. Starr ME, Ueda J, Yamamoto S, Evers BM, Saito H. The effects of aging on pulmonary oxidative damage, protein nitration, and extracellular superoxide dismutase down-regulation during systemic inflammation. Free Radic Biol Med 2011, 50:371-380. 10.1016/j.freeradbiomed.2010.11.013, 21092756.
49. Ungvari Z, Bailey-Downs L, Sosnowska D, Gautam T, Koncz P, Losonczy G, Ballabh P, de Cabo R, Sonntag WE, Csiszar A. Vascular oxidative stress in aging: a homeostatic failure due to dysregulation of NRF2-mediated antioxidant response. Am J Physiol Heart Circ Physiol 2011, 301:H363-H372. 10.1152/ajpheart.01134.2010, 21602469.
50. Ungvari Z, Bailey-Downs L, Gautam T, Sosnowska D, Wang M, Monticone RE, Telljohann R, Pinto JT, de Cabo R, Sonntag WE, Lakatta EG, Csiszar A. Age-associated vascular oxidative stress, Nrf2 dysfunction, and NF-kB activation in the nonhuman primate Macaca mulatta. J Gerontol A Biol Sci Med Sci 2011, 66:866-875. 10.1093/gerona/glr092, 21622983.
51. Saito H, Papaconstantinou J. Age-associated differences in cardiovascular inflammatory gene induction during endotoxic stress. J Biol Chem 2001, 276:29307-29312. 10.1074/jbc.M103740200, 11382779.
52. Csiszar A, Wang M, Lakatta EG, Ungvari Z. Inflammation and endothelial dysfunction during aging: role of NF-kappaB. J Appl Physiol 2008, 105:1333-1341. 10.1152/japplphysiol.90470.2008, 18599677.
53. Tucsek Z, Gautam T, Sonntag WE, Toth P, Saito H, Salomao R, Szabo C, Csiszar A, Ungvari Z. Aging exacerbates microvascular endothelial damage induced by circulating factors present in the serum of septic patients. J Gerontol A Biol Sci Med Sci 2013, 68:652-660. 10.1093/gerona/gls232, 23183901.
54. Cuzzocrea S, Zingarelli B, O'Connor M, Salzman AL, Szabo C. Effect of L-buthionine-(S, R)-sulphoximine, an inhibitor of gamma-glutamylcysteine synthetase on peroxynitrite- and endotoxic shock-induced vascular failure. Br J Pharmacol 1998, 123:525-537. 10.1038/sj.bjp.0701612, 9504394.
55. Jagtap P, Soriano FG, Virag L, Liaudet L, Mabley J, Szabo E, Hasko G, Marton A, Lorigados CB, Gallyas F, Sümegi B, Hoyt DG, Baloglu E, VanDuzer J, Salzman AL, Southan GJ, Szabo C. Novel phenanthridinone inhibitors of poly (adenosine 5'-diphosphate-ribose) synthetase: potent cytoprotective and antishock agents. Crit Care Med 2002, 30:1071-1082. 10.1097/00003246-200205000-00019, 12006805.
56. Thimmulappa RK, Lee H, Rangasamy T, Reddy SP, Yamamoto M, Kensler TW, Biswal S. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J Clin Invest 2006, 116:984-995. 10.1172/JCI25790, 16585964.
57. Murakami K, Enkhbaatar P, Shimoda K, Cox RA, Burke AS, Hawkins HK, Traber LD, Schmalstieg FC, Salzman AL, Mabley JG, Komjati K, Pacher P, Zsengeller Z, Szabo C, Traber DL. Inhibition of poly (ADP-ribose) polymerase attenuates acute lung injury in an ovine model of sepsis. Shock 2004, 21:126-133. 10.1097/01.shk.0000108397.56565.4a, 14752285.
58. Maybauer DM, Maybauer MO, Szabo C, Cox RA, Westphal M, Kiss L, Horvath EM, Traber LD, Hawkins HK, Salzman AL, Southan GJ, Herndon DN, Traber DL. The peroxynitrite catalyst WW-85 improves pulmonary function in ovine septic shock. Shock 2011, 35:148-155. 10.1097/SHK.0b013e3181eb4556, 20577150.
59. Soriano FG, Nogueira AC, Caldini EG, Lins MH, Teixeira AC, Cappi SB, Lotufo PA, Bernik MM, Zsengellér Z, Chen M, Szabo C. Potential role of poly(adenosine 5'-diphosphate-ribose) polymerase activation in the pathogenesis of myocardial contractile dysfunction associated with human septic shock. Crit Care Med 2006, 34:1073-1079. 10.1097/01.CCM.0000206470.47721.8D, 16484919.
60. Wang H, Ma S. The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome. Am J Emerg Med 2008, 26:711-715. 10.1016/j.ajem.2007.10.031, 18606328.
61. Pacher P, Szabo C. Role of the peroxynitrite-poly(ADP-ribose) polymerase pathway in human disease. Am J Pathol 2008, 173:2-13. 10.2353/ajpath.2008.080019, 18535182.
62. Moncada S, Bolaños JP. Nitric oxide, cell bioenergetics and neurodegeneration. J Neurochem 2006, 97:1676-1689. 10.1111/j.1471-4159.2006.03988.x, 16805776.
63. Brown GC. Nitric oxide and mitochondria. Front Biosci 2007, 12:1024-1033. 10.2741/2122, 17127357.
64. Larsen FJ, Schiffer TA, Weitzberg E, Lundberg JO. Regulation of mitochondrial function and energetics by reactive nitrogen oxides. Free Radic Biol Med 2012, 53:1919-1928. 10.1016/j.freeradbiomed.2012.08.580, 22989554.
65. Fink MP. Bench-to-bedside review: Cytopathic hypoxia. Crit Care 2002, 6:491-499. 10.1186/cc1824, 12493070.
66. Levy RJ. Mitochondrial dysfunction, bioenergetic impairment, and metabolic down-regulation in sepsis. Shock 2007, 28:24-28. 10.1097/01.shk.0000235089.30550.2d, 17483747.
67. Zapelini PH, Rezin GT, Cardoso MR, Ritter C, Klamt F, Moreira JC, Streck EL, Dal-Pizzol F. Antioxidant treatment reverses mitochondrial dysfunction in a sepsis animal model. Mitochondrion 2008, 8:211-218. 10.1016/j.mito.2008.03.002, 18417427.
68. Starr ME, Hu Y, Stromberg AJ, Carmical JR, Wood TG, Evers BM, Saito H. Gene expression profile of mouse white adipose tissue during inflammatory stress: age-dependent upregulation of major procoagulant factors. Aging Cell 2013, 12:194-206. 10.1111/acel.12040, 23279636.
69. Tao W, Deyo D, Traber D, Johnston W, Sherwood E. Hemodynamic and cardiac contractile function during sepsis caused by cecal ligation and puncture in mice. Shock 2004, 21:31-37. 10.1097/01.shk.0000101673.49265.5d, 14676681.