Abstract
Sepsis is one of the main causes of ICU hospitalization worldwide, with a high mortality rate, and is associated with a large number of comorbidities. One of the main comorbidities associated with sepsis is septic cardiomyopathy. This process occurs mainly due to mechanisms of damage in the cardiovascular system that will lead to changes in cardiovascular physiology, such as decreased Ca2+ response, mitochondrial dysfunction and decreased β-adrenergic receptor response. Within this process the exosomes play an important role in the pathophysiology of this disease, in which the exosomal content is related to mechanisms that will trigger its development. After platelet activation through ROS exposition, exosomes containing high concentrations of NADPH are released in heart blood vessels, those exosomes will be internalized in endothelial cells leading to cell death and cardiac dysfunction. On the opposite, exosomes derived from mesenchymal stem cells contain miR-223, that have anti-inflammatory properties, are released in less quantities in septic patients causing an imbalance that leads to cardiac dysfunction.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Dellinger R, Levy M, Rhodes A (2013) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care 41(2):580–637
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche J-D, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent J-L, Angus DC (2016) The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 315(8):801–810
Dombrovskiy VY, Martin AA, Sunderram J, Paz HL (2007) Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med 35(5):1244–1250
Remick DG (2007) Pathophysiology of sepsis. Am J Pathol 170(5):1435–1444
Fallach R, Shainberg A, Avlas O, Fainblut M, Chepurko Y, Porat E, Hochhauser E (2010) Cardiomyocyte Toll-like receptor 4 is involved in heart dysfunction following septic shock or myocardial ischemia. J Mol Cell Cardiol 48(6):1236–1244
Boomer JS, Green JM, Hotchkiss RS (2014) The changing immune system in sepsis: is individualized immuno-modulatory therapy the answer? Virulence 5(1):45–56
Jacobi J (2002) Pathophysiology of sepsis. Am J Health Syst Pharm 59(Suppl 1):S3–S8
Turner MD, Nedjai B, Hurst T, Pennington DJ (2014) Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta, Mol Cell Res 1843(11):2563–2582
Abraham E (2003) Nuclear factor-kappaB and its role in sepsis-associated organ failure. J Infect Dis 187(Suppl):S364–S369
Nakae H, Motoyama S, Kurosawa S, Inaba H (1999) The effective removal of proinflammatory cytokines by continuous hemofiltration with a polymethylmethacrylate membrane following severe burn injury: report of three cases. Surg Today 29(8):762–765
Shimaoka M, Park EJ (2008) Advances in understanding sepsis. Eur J Anaesthesiol Suppl 42:146–153
de Oliveira S, Rosowski EE, Huttenlocher A (2016) Neutrophil migration in infection and wound repair: going forward in reverse. Nat Rev Immunol 16(6):378–391
Drifte G, Dunn-Siegrist I, Tissieres P, Pugin J (2013) Innate immune functions of immature neutrophils in patients with sepsis and severe systemic inflammatory response syndrome. Crit Care Med 41(3):820–832
Bhagat K (1998) Endothelial function and myocardial infarction. Cardiovasc Res 39(2):312–317
Szent-Gyorgyi AG (1975) Calcium regulation of muscle contraction. Biophys J 15(7):707–723
Wakabayashi T (2015) Mechanism of the calcium-regulation of muscle contraction—in pursuit of its structural basis. Proc Jpn Acad Ser B Phys Biol Sci 91(7):321–350
Tavernier B, Li JM, El-Omar MM, Lanone S, Yang ZK, Trayer IP, Mebazaa A, Shah AM (2001) Cardiac contractile impairment associated with increased phosphorylation of troponin I in endotoxemic rats. FASEB J 15(2):294–296
Abi-Gerges N, Tavernier B, Mebazaa A, Faivre V, Paqueron X, Payen D, Fischmeister R, Mery PF (1999) Sequential changes in autonomic regulation of cardiac myocytes after in vivo endotoxin injection in rat. Am J Respir Crit Care Med 160(4):1196–1204
Liu S, Schreur KD (1995) G protein-mediated suppression of L-type Ca2+ current by interleukin-1 beta in cultured rat ventricular myocytes. Am J Phys 268(2 Pt 1):C339–C349
Tsai T-Y, Lou S-L, Wong K-L, Wang M-L, Su T-H, Liu Z-M, Yeh L-J, Chan P, Gong C-L, Leung Y-M (2015) Suppression of Ca(2+) influx in endotoxin-treated mouse cerebral cortex endothelial bEND.3 cells. Eur J Pharmacol 755:80–87
Zhong J, Hwang TC, Adams HR, Rubin LJ (1997) Reduced L-type calcium current in ventricular myocytes from endotoxemic guinea pigs. Am J Phys 273(5 Pt 2):H2312–H2324
Wu LL, Liu MS (1992) Altered ryanodine receptor of canine cardiac sarcoplasmic reticulum and its underlying mechanism in endotoxin shock. J Surg Res 53(1):82–90
Zhu X, Bernecker OY, Manohar NS, Hajjar RJ, Hellman J, Ichinose F, Valdivia HH, Schmidt U (2005) Increased leakage of sarcoplasmic reticulum Ca2+ contributes to abnormal myocyte Ca2+ handling and shortening in sepsis. Crit Care Med 33(3):598–604
Ayers L, Nieuwland R, Kohler M, Kraenkel N, Ferry B, Leeson P (2015) Dynamic microvesicle release and clearance within the cardiovascular system: triggers and mechanisms. Clin Sci (Lond) 129(11):915–931
Dai D-F, Rabinovitch PS, Ungvari Z (2012) Mitochondria and cardiovascular aging. Circ Res 110(8):1109–1124
Marzetti E, Csiszar A, Dutta D, Balagopal G, Calvani R, Leeuwenburgh C (2013) Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics. Am J Phys Heart Circ Phys 305(4):H459–H476
Giustarini D, Dalle-Donne I, Tsikas D, Rossi R (2009) Oxidative stress and human diseases: origin, link, measurement, mechanisms, and biomarkers. Crit Rev Clin Lab Sci 46(5–6):241–281
Reis JF, Monteiro VVS, de Souza Gomes R, do Carmo MM, da Costa GV, Ribera PC, Monteiro MC (2016) Action mechanism and cardiovascular effect of anthocyanins: a systematic review of animal and human studies. J Transl Med 14(1):315–315
Sawyer DB, Colucci WS (2000) Mitochondrial oxidative stress in heart failure. Circ Res 86(2):119–121
Singer M (2014) The role of mitochondrial dysfunction in sepsis-induced multi-organ failure. Virulence 5(1):66–72
Cimolai MC, Alvarez S, Bode C, Bugger H (2015) Mitochondrial mechanisms in septic cardiomyopathy. Int J Mol Sci 16(8):17763–17778
Wachter SB, Gilbert EM (2012) Beta-adrenergic receptors, from their discovery and characterization through their manipulation to beneficial clinical application. Cardiology 122(2):104–112
Johnson M (2006) Molecular mechanisms of beta(2)-adrenergic receptor function, response, and regulation. J Allergy Clin Immunol 117(1):18–24. Quiz 25
Strosberg AD (1993) Structure, function, and regulation of adrenergic receptors. Protein Sci 2(8):1198–1209
Hahn PY, Wang P, Tait SM, Ba ZF, Reich SS, Chaudry IH (1995) Sustained elevation in circulating catecholamine levels during polymicrobial sepsis. Shock 4(4):269–273
Reithmann C, Hallstrom S, Pilz G, Kapsner T, Schlag G, Werdan K (1993) Desensitization of rat cardiomyocyte adenylyl cyclase stimulation by plasma of noradrenaline-treated patients with septic shock. Circ Shock 41(1):48–59
Matsuda N, Hattori Y, Akaishi Y, Suzuki Y, Kemmotsu O, Gando S (2000) Impairment of cardiac beta-adrenoceptor cellular signaling by decreased expression of G(s alpha) in septic rabbits. Anesthesiology 93(6):1465–1473
Wu L-L, Yang S-L, Yang R-C, Hsu H-K, Hsu C, Dong L-W, Liu M-S (2003) G protein and adenylate cyclase complex-mediated signal transduction in the rat heart during sepsis. Shock 19(6):533–537
Gilbert EM, Olsen SL, Renlund DG, Bristow MR (1993) beta-Adrenergic receptor regulation and left ventricular function in idiopathic dilated cardiomyopathy. Am J Cardiol 71(9):23C–29C
Boyd JH, Mathur S, Wang Y, Bateman RM, Walley KR (2006) Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-kappaB dependent inflammatory response. Cardiovasc Res 72(3):384–393
Essandoh K, Fan G-C (2014) Role of extracellular and intracellular microRNAs in sepsis. Biochim Biophys Acta 1842(11):2155–2162
Barry OP, Praticò D, Savani RC, FitzGerald GA (1998) Modulation of monocyte-endothelial cell interactions by platelet microparticles. J Clin Investig 102(1):136–144
Weber A-A, Köppen HO, Schrör K (2000) Platelet-derived microparticles stimulate coronary artery smooth muscle cell mitogenesis by a PDGF-independent mechanism. Thromb Res 98(5):461–466
Nieuwland R, Berckmans RJ, McGregor S, Böing AN, Romijn FP, Westendorp RG, Hack CE, Sturk A (2000) Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood J 95(3):930–935
Ogura H, Kawasaki T, Tanaka H, Koh T, Tanaka R, Ozeki Y, Hosotsubo H, Kuwagata Y, Shimazu T, Sugimoto H (2001) Activated platelets enhance microparticle formation and platelet-leukocyte interaction in severe trauma and sepsis. J Trauma Acute Care Surg 50(5):801–809
Irani K (2000) Oxidant signaling in vascular cell growth, death, and survival. Circ Res 87:179–183
Finazzi-Agrò A, Menichelli A, Persiani M, Biancini G, Del Principe D (1982) Hydrogen peroxide release from human blood platelets. Biochim Biophys Acta Gen Subj 718(1):21–25
Leoncini G, Maresca M, Colao C (1991) Oxidative metabolism of human platelets. Biochem Int 25(4):647–655
Marcus AJ, Silk ST, Safier LB, Ullman HL (1977) Superoxide production and reducing activity in human platelets. J Clin Invest 59:149–158
Janiszewski M, Do Carmo AO, Ma P, Silva E, Knobel E, Laurindo FRM (2004) Platelet-derived exosomes of septic individuals possess proapoptotic NAD(P)H oxidase activity: a novel vascular redox pathway. Crit Care Med 32(3):818–825
Caccese D, Praticò D, Ghiselli A, Natoli S, Pignatelli P, Sanguigni V, Iuliano L, Violi F (2000) Superoxide anion and hydroxyl radical release by collagen-induced platelet aggregation—role of arachidonic acid metabolism. Thromb Haemost 83(3):485–490
Azevedo LCP, Janiszewski M, Pontieri V, Pedro MA, Bassi E, Tucci PJF, Laurindo FRM (2007) Platelet-derived exosomes from septic shock patients induce myocardial dysfunction. Crit Care 11(6):R120–R120
Kumar A, Haery C, Parrillo JE (2001) Myocardial dysfunction in septic shock: part I. Clinical manifestation of cardiovascular dysfunction. J Cardiothorac Vasc Anesth 15(3):364–376
Paulus WJ, Bronzwaer JGF (2002) Myocardial contractile effects of nitric oxide. Heart Fail Rev 7(4):371–383
Ullrich R, Scherrer-Crosbie M, Bloch KD, Ichinose F, Nakajima H, Picard MH, Zapol WM, Quezado ZM (2000) Congenital deficiency of nitric oxide synthase 2 protects against endotoxin-induced myocardial dysfunction in mice. Circulation 102(12):1440–1446
Ferdinandy P, Danial H, Ambrus I, Rothery RA, Schulz R (2000) Peroxynitrite is a major contributor to cytokine-induced myocardial contractile failure. Circ Res 87(3):241–247
Gambim MH, do Carmo Ade O, Marti L, Verissimo-Filho S, Lopes LR, Janiszewski M (2007) Platelet-derived exosomes induce endothelial cell apoptosis through peroxynitrite generation: experimental evidence for a novel mechanism of septic vascular dysfunction. Crit Care 11(5):R107–R107
Zhu C, Wang X, Qiu L, Peeters-Scholte C, Hagberg H, Blomgren K (2004) Nitrosylation precedes caspase-3 activation and translocation of apoptosis-inducing factor in neonatal rat cerebral hypoxia-ischaemia. J Neurochem 90(2):462–471
Albina JE, Cui S, Mateo RB, Reichner JS (1993) Nitric oxide-mediated apoptosis in murine peritoneal macrophages. J Immunol 150(11):5080–5085
Rössig L, Fichtlscherer B, Breitschopf K, Haendeler J, Zeiher AM, Mülsch A, Dimmeler S (1999) Nitric oxide inhibits caspase-3 by S-nitrosation in vivo. J Biol Chem 274(11):6823–6826
Humphreys DT, Westman BJ, Martin DIK, Preiss T (2005) MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function. Proc Natl Acad Sci U S A 102(47):16961–16966
Fabian MR, Sonenberg N (2012) The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol 19(6):586–593
Jackson RJ, Standart N (2007) How do microRNAs regulate gene expression? Sci STKE 367(367):re1
Sayed D, Abdellatif M (2011) MicroRNAs in development and disease. Physiol Rev 91(3):827–887
Zhu H, Fan G-C (2011) Extracellular/circulating microRNAs and their potential role in cardiovascular disease. Am J Cardiovasc Dis 1(2):138–149
Zhu H, Fan G-C (2012) Role of microRNAs in the reperfused myocardium towards post-infarct remodelling. Cardiovasc Res 94(2):284–292
Wang H, Zhang P, Chen W, Feng D, Jia Y, Xie L (2012) Serum microRNA signatures identified by Solexa sequencing predict sepsis patients’ mortality: a prospective observational study. PLoS One 7(6):e38885
Benz F, Roy S, Trautwein C, Roderburg C, Luedde T (2016) Circulating microRNAs as biomarkers for sepsis. Int J Mol Sci 17(78):1–17
Taïbi F, Meuth VM-l, Massy ZA, Metzinger L (2014) miR-223 : an inflammatory oncomiR enters the cardiovascular field. Biochim Biophys Acta 1842:1001–1009
Wang X, Huang W, Yang Y, Wang Y, Peng T, Chang J, Caldwell CC, Zingarelli B, Fan GC (2014) Loss of duplexmiR-223 (5p and 3p) aggravates myocardial depression and mortality in polymicrobial sepsis. Biochim Biophys Acta Mol Basis Dis 1842(5):701–711
Akira S, Nishio Y, Inoue M, Wang X-J, We S, Matsusaka T, Yoshida K, Sudo T, Naruto M, Kishimoto T (1994) Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell 77(1):63–71
Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS, Dong C (2007) STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 282(13):9358–9363
Ieda M, Kanazawa H, Kimura K, Hattori F, Ieda Y, Taniguchi M, Lee J-K, Matsumura K, Tomita Y, Miyoshi S, Shimoda K, Makino S, Sano M, Kodama I, Ogawa S, Fukuda K (2007) Sema3a maintains normal heart rhythm through sympathetic innervation patterning. Nat Med 13(5):604–612
Tabet F, Vickers KC, Cuesta Torres LF, Wiese CB, Shoucri BM, Lambert G, Catherinet C, Prado-Lourenco L, Levin MG, Thacker S, Sethupathy P, Barter PJ, Remaley AT, Rye K-A (2014) HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells. Nat Commun 5:3292–3292
Wang X, Gu H, Qin D, Yang L, Huang W, Essandoh K, Wang Y, Caldwell CC, Peng T, Zingarelli B, Fan G-C (2015) Exosomal miR-223 contributes to mesenchymal stem cell-elicited cardioprotection in polymicrobial sepsis. Sci Rep 5:1–16
Conflicts of Interest
The authors declare no conflicts of interest in relation to this article.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Monteiro, V.V.S., Reis, J.F., de Souza Gomes, R., Navegantes, K.C., Monteiro, M.C. (2017). Dual Behavior of Exosomes in Septic Cardiomyopathy. In: Xiao, J., Cretoiu, S. (eds) Exosomes in Cardiovascular Diseases. Advances in Experimental Medicine and Biology, vol 998. Springer, Singapore. https://doi.org/10.1007/978-981-10-4397-0_7
Download citation
DOI: https://doi.org/10.1007/978-981-10-4397-0_7
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-10-4396-3
Online ISBN: 978-981-10-4397-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)