Abstract
The heat shock proteins (HSPs) are members of highly conserved families of molecular chaperones that have multiple roles in vivo. We discuss the HSPs in general, and Hsp70 and Hsp27 in particular, and their rapid induction by severe stress in the context of tissue and organ expression in physiology and disease. We describe the current state of knowledge of the relationship and interactions between extra- and intracellular HSPs and describe mechanisms and significance of extracellular expression of HSPs. We focus on the role of the heat shock proteins as biomarkers of central nervous system (CNS) ischemia and other severe stressors and discuss recent and novel technologies for rapid measurement of proteins in vivo and ex vivo. The HSPs are compared to other proposed small molecule biomarkers for detection of CNS injury and to other methods of detecting brain and spinal cord ischemia in real time. While other biomarkers may be of use in prognosis and in design of appropriate therapies, none appears to be as rapid as the HSPs; therefore, no other measurement appears to be of use in the immediate detection of ongoing severe ischemia with the intention to immediately intervene to reduce the severity or risk of permanent damage.
Similar content being viewed by others
References
Anderson RE, Hansson LO, Nilsson O, Dijlai-Merzoug R, Settergren G (2001) High serum S100B levels for trauma patients without head injuries. Neurosurgery 48:1255–1258
Asea A (2007) Mechanisms of HSP72 release. J Biosci 32:579–584
Asea A (2008) Heat shock proteins and toll-like receptors. Handb Exp Pharmacol 183:111–127
Asea A, Jean-Pierre C, Kaur P, Rao P, Linhares IM, Skupski D, Witkin SS (2008) Heat shock protein-containing exosomes in mid-trimester amniotic fluids. J Reprod Immunol 79:12–17
Awad H, Suntres Z, Heijmans J, Smeak D, Bergdall-Costell V, Christofi FL, Magro C, Oglesbee M (2008) Intracellular and extracellular expression of the major inducible 70kDa heat shock protein in experimental ischemia-reperfusion injury of the spinal cord. Exp Neurol 212:275–284
Basu S, Hellberg A, Ulus AT, Westman J, Karacagil S (2001) Biomarkers of free radical injury during spinal cord ischemia. FEBS Lett 508:36–38
Bausero M, Gastpar R, Multhoff G, Asea A (2005) Alternative mechanism by which IFN-y enhances tumor recognition: active release of heat shock protein 72. J Immunol 175:2900–2912
Becker ST, Wendel HP, Vonthein R, Rennekampff HO, Aebert H (2007) Inducible HSP70 levels in thoracic wound fluid indicate myocardial damage after open heart surgery. J Cardiovasc Surg Torino 48:233–237
Beere HM (2005) Death versus survival: functional interaction between the apoptotic and stress-inducible heat shock protein pathways. J Clin Investig 115:2633–2639
Bickerstaff LK, Pairolero PC, Hollier LH, Melton LJ, Van Peenen HJ, Cherry KJ, Joyce JW, Lie JT (1982) Thoracic aortic aneurysms: a population-based study. Surgery 92:1103–1108
Birnie DH, Vickers LE, Hillis WS, Norrie J, Cobbe SM (2005) Increased titres of anti-human heat shock protein 60 predict an adverse 1 year prognosis in patients with acute cardiac chest pain. Heart 91:1148–1153
Blake MJ, Udelsman R, Feulner GJ, Norton DD, Holbrook NJ (1991) Stress-induced heat shock protein 70 expression in adrenal cortex: an adrenocorticotropic hormone-sensitive, age-dependent response. PNAS 88:9873–9877
Boehm AK, Saunders A, Werner J, Lis JT (2003) Transcription factor and polymerase recruitment, modification, and movement on dhsp70 in vivo in the minutes following heat shock. Mol Cell Biol 23:7628–7637
Brock MV, Redmond JM, Ishiwa S, Johnston MV, Baumgartner WA, Laschinger JC, Williams GM (1997) Clinical markers in CSF for determining neurologic deficits after thoracoabdominal aortic aneurysm repairs. Ann Thorac Surg 64:999–1003
Burbelo PD, Issa AT, Ching KH, Cohen JI, Iadarola MJ, Marques A (2010) Rapid, simple, quantitative, and highly sensitive antibody detection for Lyme disease. Clin Vaccine Immunol 17:904–909
Burton RE, White EJ, Foss TR, Phillips KM, Meltzer RH, Kojanian N, Kwok LW, Lim A, Pellerin NL, Mamaeva NV, Gilmanshin R (2010) A microfluidic chip-compatible bioassay based on single-molecule detection with high sensitivity and multiplexing. Lab Chip 10:843–851
Cambria RP, Clouse WD, Davison JK, Dunn PF, Corey M, Dorer D (2002) Thoracoabdominal aneurysm repair: results with 337 operations performed over a 15-year interval. Ann Surg 236:471–479
Carmel JB, Kakinohana O, Mestril R, Young W, Marsala M, Hart RP (2004) Mediators of ischemic preconditioning identified by microarray analysis of rat spinal cord. Exp Neurol 185:81–96
Chalworapongsa T, Erez O, Kusanovic JP, Vaisbuch E, Mazaki-Tovi S, Gotsch F, Than NG, Mittal P, Kim YM, Camacho N, Edwihn S, Gomez R, Hassan SS, Romero R (2008) Amniotic fluid heat shock protein 70 concentration in histologic chorioamnionitis, term and preterm parturition. J Matern Fetal Neonatal Med 21:449–461
Chen Y, Voegeli TS, Liu PP, Noble EG, Currie RW (2007) Heat shock paradox and a new role of heat shock proteins and their receptors as anti-inflammation targets. Inflamm Allergy Drug Targets 6:91–100
Cheung AT, Weiss SJ, McGarvey ML, Stecker MM, Hogan MS, Escherich A, Bavaria JE (2002) Interventions for reversing delayed-onset postoperative paraplegia after thoracic aortic reconstruction. Ann Thorac Surg 74:413–419
Cina CS, Abouzahr L, Arena GO, Lagana A, Devereaux PJ, Farrokhyar F (2004) Cerebrospinal fluid drainage to prevent paraplegia during thoracic and thoracoabdominal aortic aneurysm surgery: a systematic review and meta-analysis. J Vasc Surg 40:36–44
Cizkova D, Carmel JB, Yamamoto K, Kakinohana O, Sun D, Hart RP, Marsala M (2004) Characterization of spinal HSP72 induction and development of ischemic tolerance after spinal ischemia in rats. Exp Neurol 185:97–108
Cizkova D, Lukacova N, Marsala M, Kafka J, Lukac I, Jergova S, Cizek M, Marsala J (2005) Experimental cauda equina compression induces HSP70 synthesis in dog. Physiol Res 54:349–356
Connolly JE (1998) Hume memorial lecture. Prevention of spinal cord complications in aortic surgery. Am J Surg 176:92–101
Coselli JS, LeMaire SA, Koksoy C, Schmittling ZC, Curling PE (2002) Cerebrospinal fluid drainage reduces paraplegia after thoracoabdominal aortic aneurysm repair: results of a randomized clinical trial. J Vasc Surg 35:631–639
Cowan JA Jr, Dimick JB, Henke PK, Huber TS, Stanley JC, Upchurch GR Jr (2003) Surgical treatment of intact thoracoabdominal aortic aneurysms in the United States: hospital and surgeon volume-related outcomes. J Vasc Surg 37:1169–1174
Crawford ES, Crawford JL, Safi HJ, Coselli JS, Hess KR, Brooks B, Norton HJ, Glaeser DH (1986) Thoracoabdominal aortic aneurysms: preoperative and intraoperative factors determining immediate and long term results of operation in 605 patients. J Vasc Surg 3:389–404
Da Rocha AB, Zanoni C, De Freitas GR, Andre C, Himelfarb S, Schneider RF, Grivicich I, Borges L, Schwartsmann G, Kaufmann M, Regner A (2005) Serum Hsp70 as an early predictor of fatal outcome after severe traumatic brain injury in males. J Neurotrauma 22:966–977
Dalsgaard MK, Ott P, Dela F, Juul A, Pedersen BK, Warberg J, Fahrenkrug J, Secher NH (2004) The CSF and arterial to internal jugular venous hormonal differences during exercise in humans. Exp Physiol 89:271–277
Daugaard M, Rohde M, Jaattela M (2007) The heat shock protein family: highly homologous proteins with overlapping and distinct functions. FEBS Lett 581:3702–3710
de Haan P, Kalkman CJ (2001) Spinal cord monitoring: somatosensory- and motor-evoked potentials. Anesthesiol Clin N Am 19:923–945
de Jong PR, Schadenberg AW, Jansen NJ, Prakken BJ (2009) Hsp70 and cardiac surgery: molecular chaperone and inflammatory regulator with compartmentalized effects. Cell Stress Chaperones 14:117–131
Denda S, Taneoka M, Honda H, Watanabe Y, Imai H, Kitahara Y (2006) Prolonged loss of leg myogenic motor evoked potentials during thoracoabdominal aortic aneurysm repair, without postoperative paraplegia. J Anesthesiol 20:314–318
Dong CC, MacDonald DB, Janusz MT (2002) Intraoperative spinal cord monitoring during descending thoracic and thoracoabdominal aneurysm surgery. Ann Thorac Surg 74:S1873–S1876
Dybdahl B, Wahba A, Haaverstad R, Kirkeby-Garstad I, Kierulf P, Espevik T, Sundan A (2004) On-pump versus off-pump coronary artery bypass grafting: more heat-shock protein 70 is released after on-pump surgery. Eur J Cardiothorac Surg 25:985–992
Feige U, Polla BS (1994) Heat shock proteins: the hsp 70 family. Experientia 50:979–986
Feige U, Morimoto RI, Yahara I, Polla BS (eds) (1996) Stress-inducible cellular responses, 1st edn. Birkhauser, Basel
Forsdyke DR (1999) Heat shock proteins as mediators of aggregation-induced ‘danger’ signals: implications of the slow evolutionary fine-tuning of sequences for the antigenicity of cancer cells. Cell Stress Chaperones 4:205–210
Frassdorf J, De Hert S, Schlack W (2009) Anaesthesia and myocardial ischaemia/reperfusion injury. Br J Anaesth 103:89–98
Galla JD, Ergin MA, Lansman SL, McCullough JN, Nguyen KH, Spielvogel D, Klein JJ, Griepp RB (1999) Use of somatosensory evoked potentials for thoracic and thoracoabdominal aortic resections. Ann Thorac Surg 67:1947–1958
Ghayour-Mobarhan M, Sahebkar A, Parizadeh SM, Moohebati M, Tavallaie S, Rezajazemi-Bajestani SM, Esmaelli HA, Ferns G (2008) Antibody titres to heat shock protein 27 are elevated in patients with acute coronary syndrome. Int J Exp Pathol 89:209–215
Gilby KL, Armstrong JN, Currie RW, Robertson HA (1997) The effects of hypoxia-ischemia on expression of c-Fos, c-Jun and Hsp70 in the young rat hippocampus. Mol Brain Res 48:87–96
Gloviczki P (2002) Surgical repair of thoracoabdominal aneurysms: patient selection, techniques and results. Cardiovasc Surg 10:434–441
Graner MW, Raynes DA, Bigner DD, Guerriero V (2009) Heat shock protein 70-binding protein 1 is highly expressed in high-grade gliomas, interacts with multiple heat shock protein 70 family members, and specifically binds brain tumor cell surfaces. Cancer Sci 100:1870–1879
Gruden G, Bruno G, Chaturvedi N, Burt D, Schalkwijk C, Pinach S, Stehouwer CD, Witte DR, Fuller JH, Perin PC, EURODIAB Prospective Complications Study Group (2008) Serum heat shock protein 27 and diabetes complications in the EURODIAB prospective complications study: a novel circulating marker for diabetic neuropathy. Diabetes 57:1966
Guerit JM, Witdoeckt C, Verhelst R, Matta AJ, Jacquet LM, Dion RA (1999) Sensitivity, specificity, and surgical impact of somatosensory evoked potentials in descending aorta surgery. Ann Thorac Surg 67:1943–1946
Hamilton IN Jr, Hollier LH (1998) Adjunctive therapy for spinal cord protection during thoracoabdominal aortic aneurysm repair. Semin Thorac Cardiovasc Surg 10:35–39
Hasselblatt M, Mooren FC, von Ahsen N, Keyvani K, Fromme A, Schwarze-Eicker K, Senner V, Paulus W (2004) Serum S100beta increases in marathon runners reflect extracranial release rather than glial damage. Neurology 62:1634–1636
Haun JB, Yoon TJ, Lee H, Weissleder R (2010) Magnetic nanoparticle biosensors. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2:291–304
Hecker JG, Sundram H, Zou S, Praestgaard A, Bavaria JE, Ramchandren S, McGarvey ML (2008) Heat shock proteins HSP70 and 27 in the cerebral spinal fluid of patients undergoing thoracic aneurysm repair correlate with the probability of post-op paralysis. Cell Stress Chaperones 13:435–446
Hightower LE, Guidon PT (1989) Selective release from cultured mammalian cells of heat shock (stress) proteins that resemble glia-axon transfer proteins. J Cell Physiol 138:257–266
Hu S, Dong H-l, Li Y-z, Luo Z-j, Sun L, Yang Q-z, Yang L-f, Xiong L (2010) Effects of remote ischemic preconditioning on biochemical markers and neurologic outcomes in patients undergoing elective cervical decompression surgery. A prospective randomized controlled trial. J Neurosurg Anesthesiol 22:46–52
Hughes AJ, Herr AE (2010) Quantitative enzyme activity determination with zeptomole sensitivity by microfluidic gradient-gel zymography. Anal Chem 82:3803–3811
Jacobs MJ, de Mol BA, Elenbaas T, Mess WH, Kalkman CJ, Schurink GW, Moctar B (2002) Spinal cord blood supply in patients with thoracoabdominal aortic aneurysms. J Vasc Surg 35:30–37
Jacobs MJ, Mess W, Mochtar B, Nijenhuis RJ, Statius van Epps RG, Schurink GW (2006) The value of motor evoked potentials in reducing paraplegia during thoracoabdominal aneurysm repair. J Vasc Surg 43:239–246
Jiang KW, Yang CW, Shui QX, Xia (1991) Time course of mu-calpain activation, c-Fos, c-Jun, HSP70 and HSP27 expression in hypoxic-ischemic neonatal rat brain (Chinese). Zhonghua Er Ke Zhi 42:441–445
Joly AL, Wettstein G, Mignot G, Ghiringhelli F, Garrido C (2010) Dual role of heat shock proteins as regulators of apoptosis and innate immunity. J Innate Immun 2(3):238–247
Kakinohana M, Nakamura S, Fuchigami T, Sugahara K (2007) Transcranial motor-evoked potentials monitoring can detect spinal cord ischemia more rapidly than spinal cord-evoked potentials monitoring during aortic occlusion in rats. Eur Spine J 16:787–793
Kampinga HH, Hageman J, Vos MJ, Kubota H, Tanguay RM, Bruford EA, Cheetman ME, Chen B, Hightower LE (2010) Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones 14:105–111
Katz NM, Blackstone EH, Kirklin JW, Karp RB (1981) Incremental risk factors for spinal cord injury following operation for acute traumatic aortic transection. J Thorac Cardiovasc Surg 81:669–674
Kawanishi Y, Munakata H, Matsumori M, Tanaka H, Yamashita T, Nakagiri K, Okada K, Okita Y (2007) Usefulness of transcranial motor evoked potentials during thoracoabdominal aortic surgery. Ann Thorac Surg 83:456–461
Keller A, Leidinger P, Borries A, Wendschlag A, Wucherpfennig F, Scheffler M, Huwer H, Lenhof H-P, Meese E (2009) miRNAs in lung cancer- studying complex fingerprints in patient’s blood cells by microarray experiments. BMC Cancer 9:353
Khan SN, Stansby G (2003) Cerebrospinal fluid drainage for thoracic and thoracoabdominal aortic aneurysm surgery. Cochrane Database Syst Rev 1:CD003635
Kim D, Ouyang H, Li GC (1995) Heat shock protein hsp70 accelerates the recovery of heat-shocked mammalian cells through its modulation of heat shock transcription factor HSF1. Proc Natl Acad Sci 92:2126–2130
Kleine TO, Benes L, Zofel P (2003) Studies of the brain specificity of S100B and neuron-specific enolase (NSE) in blood serum of acute care patients. Brain Res Bull 61:265–279
Lancaster GI, Febbraio MA (2005a) Exosome-dependent trafficking of HSP70: a novel secretory pathway for cellular stress proteins. J Biol Chem 280:23349–23355
Lancaster GI, Febbraio MA (2005b) Mechanisms of stress-induced cellular HSP72 release: implications for exercise-induced increases in extracellular HSP72. Exerc Immunol Rev 11:46–52
Lancaster GI, Moller K, Nielsen B, Secher NH, Febbraio MA, Nybo L (2004) Exercise induces the release of heat shock protein from the human brain in vivo. Cell Stress Chaperones 9:276–280
Latchman DS (2005) HSP27 and cell survival in neurones. Int J Hyperthermia 21:393–402
Lee KS, Chung JH, Oh BH, Hong CH (2008) Increased plasma levels of heat shock protein 70 in patients with vascular mild cognitive impairment. Neurosci Lett 436:223–226
Lehnardt S, Schott E, Trimbuch T, Laubisch D, Krueger C, Wulczyn G, Nitsch R, Weber JR (2008) A vicious cycle involving release of heat shock protein 60 from injured cells and activation of toll-like receptor 4 mediates neurodegeneration in the CNS. J Neurosci 28:2320–2331
Lewis ME, Ranasinghe AM, Revell MP, Bonser RS (2002) Surgical repair of ruptured thoracic and thoracoabdominal aortic aneurysms. Br J Surg 89:442–445
Li D, Duncan RF (1995) Transient acquired thermotolerance in Drosophila, correlated with rapid degradation of Hsp70 during recovery. Eur J Biochem 231:454–465
Li D-P, Calzi SL, Sanchez SR (1999) Inhibition of heat shock factor activity prevents heat shock potentiation of glucocorticoid receptor-mediated gene expression. Cell Stress Chaperones 4:223–234
Li Z, Zhao X, Wei Y (2004) Regulation of apoptotic signal transduction pathways by the heat shock proteins. Sci China C Life Sci 47:107–114
Lindsay TF, Luo XP, Lehotay DC, Rubin BB, Anderson M, Walker PM, Romaschin AD (1999) Ruptured abdominal aortic aneurysm, a “two-hit” ischemia/reperfusion injury: evidence from an analysis of oxidative products. J Vasc Surg 30:219–228
Lipcsey M, Olovsson M, Larsson E, Einarsson R, Qadhr GA, Sjolin J, Larsson A (2010) The brain is a source of S100B increase during endotoxemia in the pig. Anesth Analg 110:174–180
Liu D-Z, Tian Y, Ander BP, Xu H, Stamova BS, Zhan X, Turner RJ, Jickling G, Sharp FR (2010) Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures. J Cereb Blood Flow Metab 30:92–101
Livesay JJ, Cooley DA, Ventemiglia RA, Montero CG, Warrian RK, Brown DM, Duncan JM (1985) Surgical experience in descending thoracic aneurysmectomy with and without adjuncts to avoid ischemia. Ann Thorac Surg 39:37–46
Madach K, Molvarec A, RIgo J, Nagy B, Penzes I, Karadi I, Prohaszka Z (2010) Elevated serum 70 kDa heat shock protein level reflects tissue damage and severity in the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Eur J Obstet Gynecol Reprod Biol 139:133–138
Mambula SS, Stevenson MA, Ogawa K, Calderwood SK (2007) Mechanisms for Hsp70 secretion: crossing membranes without a leader. Methods 43:168–175
Mandal K, Torsney E, Polonieki J, Camm AJ, Xu Q, Jahangiri M (2005) Association of high intracellular, but not serum, heat shock proteins 70 with postoperative atrial fibrillation. Ann Thorac Surg 79:865–871
Mariucci G, Tantucci M, Giuditta A, Ambrosini MV (2007) Permanent brain ischemia induces marked increments in hsp72 expression and local protein synthesis in synapses of the ischemic hemisphere. Neurosci Lett 415:77–80
McGarvey ML, Cheung AT, Szeto W, Messe SR (2007) Management of neurologic complications of thoracic aortic surgery. J Clin Neurophysiol 24:336–343
Messe SR, Bavaria JE, Mullen M, Cheung AT, Davis R, Gutsche J, Woo EY, Szeto WY, Pochettino A, Woo YJ, Kasner SE, McGarvey ML (2008) Neurological outcomes from high risk descending thoracic and thoracoabdominal aortic operations in the era of endovascular repair. Neurocrit Care 9:344–351
Milner CM, Campbell RD (1990) Structure and expression of the three MHC-linked HSP70 genes. Immunogenetics 32:242–251
Minowada G, Welch WJ (1995) Clinical implications of the stress response. J Clin Invest 95:3–12
Modesti PA, Gamberi T, Bazzini C, Borro M, Romano SM, Cambi GE, Corvi A, Dorigo W, Paparella L, Pratesi C, Carini M, Gensini GF, Modesti A (2009) Response of serum proteome in patients undergoing infrarenal aortic aneurysm repair. Anesth 111:844–854
Molvarec A, RIgo J, Lazar L, Balogh K, Mako V, Cervenak L, Mezes M, Prohaska Z (2009) Increased serum heat-shock protein 70 levels reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia. Cell Stress Chaperones 14:151–159
Molvarec A, Tamasi L, Losonczy G, Madach K, Prohaska Z, RIgo J (2010) Circulating heat shock protein 70 (HSPA1A) in normal and pathological pregnancies. Cell Stress Chaperones 15:237–247
Morimoto RI, Tissieres A, Georgopoulos C (eds) (1994) The biology of heat shock proteins and molecular chaperones. Cold Spring Harbor Laboratory, Plainview
Multhoff G (2007) Heat shock protein 70 (Hsp70): membrane location, export and immunological significance. Methods 43:229–237
Munell F, Burke RE, Bandele A, Gubits RM (1994) Localization of c-fos, c-jun, and hsp70 mRNA expression in brain after neonatal hypoxia-ischemia. Brain Res Dev Brain Res 77:111–121
Munge BS, Fisher J, Millord LN, Krause CE, Dowd RS, Rusling JF (2010) Sensitive electrochemical immunosensor for matrix metalloproteinase-3 based on single-wall carbon nanotubes. Analyst 135:1345–1350
Nagy G, Dzsinich C, Selmeci L, Sepa G, Dzsinich M, Kekesi V, Juhasz-Nagy A (2002) Biochemical alterations in cerebrospinal fluid during thoracoabdominal aortic cross-clamping in dogs. Ann Vasc Surg 16:436–441
Nienaber CA, Rousseau H, Eggebrecht H, Kische S, Fattori R, Rehders TC, Kundt G, Scheinert D, Czerny M, Kleinfeldt T, Zipfel B, Labrousse L, Ince H, Instead Trial (2009) Randomized comparison of strategies for Type B aortic dissection. The Investigation of STEnt grafts in Aortic Dissection (INSTEAD) trial. Circulation 120:2519–2528
Nowak TS Jr, Jacewicz M (1994) The heat shock/stress response in focal cerebral ischemia. Brain Pathol 4:67–76
Oh K, Lee S, Seo J, Lee D, Kim T (2010) Rapid serodiagnosis with the use of surface plasmon resonance imaging for the detection of antibodies against major surface protein A of Mycoplasma synoviae in chickens. Can J Vet Res 74:71–74
Olsson C, Thelin S, Stahle E, Ekbom A, Granath F (2006) Thoracic aortic aneurysm and dissection: increasing prevalence and improved outcomes reported in a nationwide population-based study of more than 14, 000 cases from 1987 to 2002. Circulation 114:2611–2618
Patel YJ, Payne Smith MD, de Belleroche J, Latchman DS (2005) Hsp27 and Hsp70 administered in combination have a potent protective effect against FALS-associated SOD1-mutant-induced cell death in mammalian neuronal cells. Brain Res Mol Brain Res 134:256–274
Perdrizet GA (1997) Heat shock response and organ preservation: models of organ conditioning, 1st edn. Landes, Austin
Pittet JF, Lee H, Morabito D, Howard MB, Welch WJ, Mackersie RC (2002) Serum levels of Hsp72 measured early after trauma correlate with survival. J Trauma 52:611–617
Pizon MT, Gburek T, Pizon M, Sztefko K (2006) Kinetics of plasma heat shock protein HSP-70 release in coronary artery surgery: on-pump versus off-pump. Minerva Chir 61:483–491
Pockley AG, Muthana M, Calderwood SK (2008) The dual immunoregulatory roles of stress proteins. Trends Biochem Sci 33:71–79
Pouw MH, Hosman AJ, van Middendorp JJ, Verbeek MM, Vos PE, van de Meent H (2009) Biomarkers in spinal cord injury. Spinal Cord 47:519–525
Pratico D, Iuliano L, Amerio G, Tang LX, Rokach J, Sabatino G, Violi F (2000a) Down’s syndrome is associated with increased 8, 12-iso-iPF2alpha-VI levels: evidence for enhanced lipid peroxidation in vivo. Ann Neurol 48:795–798
Pratico D, Clark CM, Lee VM, Tojanowski JQ, Rokach J, Fitzgerald GA (2000b) Increased 8, 12-iso-iPF2alpha-VI in Alzheimer’s disease: correlation of a non-invasive index of lipid peroxidation with disease severity. Ann Neurol 48:809–812
Rectenwald JE, Huber TS, Martin TD, Ozaki CK, Devidas M, Welborn MB, Seeger JM (2002) Functional outcome after thoracoabdominal aortic aneurysm repair. J Vasc Surg 35:640–647
Rigberg DA, McGory ML, Zingmond DS, Maggard MA, Agustin M, Lawrence PF, Ko CY (2006) Thirty-day mortality statistics underestimate the risk of repair of thoracoabdominal aortic aneurysms: a statewide experience. J Vasc Surg 43:217–222
Rijsdijk M, Ferrier C, Laman M, Kesecioglu J, Stam K, Slooter A (2009) Detection of ischemic electroencephalography changes during carotid endarterectomy using synchronization likelihood analysis. J Neurosurg Anesthesiol 21:302–306
Robertazzi RR, Cunningham JN Jr (1998) Intraoperative adjuncts of spinal cord protection. Semin Thorac Cardiovasc Surg 10:29–34
Rosenberg GA (2002) Matrix metalloproteinases in neuroinflammation. Glia 39:279–291
Routsi C, Stamataki E, Nanas S, Psachoulia C, Stathopoulos A, Koroneos A, Zervou M, Jullien G, Roussos C (2006) Increased levels of serum S100B protein in critically ill patients without brain injury. Shock 26:20–24
Safi HJ, Miller CC III (1999) Spinal cord protection in descending thoracic and thoracoabdominal aortic repair. Ann Thorac Surg 67:1937–1939
Schmitt JP, Schunkert H, Birnbaum DE, Aebert H (2002) Kinetics of heat shock protein 70 synthesis in the human heart after cold cardioplegic arrest. Eur J Cardio-Thorac Surg 22:415–420
Sedlak BJ (1996) Heat shock proteins finding a broad range of clinical uses and applications. Genet Eng News 16:6
Selkirk GA, McLellan TM, Wright HE, Rhind SG (2009) Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional stress in trained and untrained individuals. Am J Physiol Integr Comp Physiol 296:R575–R586
Sharp FS, Massa SM, Swanson RA (1999) Heat-shock protein protection. Trends Neurol Sci TINS 22:96–99
Shine TSJ, Harrison BA, De Ruyter ML, Crook JE, Heckman M, Daube JR, Stapefeldt WH, Cherry KJ, Glovicki P, Bower TC, Murray MJ (2008) Motor and somatosensory evoked potentials. Anesthesiology 108:580–587
Siman R, McIntosh TK, Soltesz KM, Chen Z, Neumar RW, Roberts VL (2004) Proteins released from degenerating neurons are surrogate markers for acute brain damage in the rat. Neurobiol Dis 16:311–320
Siman R, Zhang C, Roberts VL, Pitts-Kiefer A, Neumar RW (2005) Novel surrogate markers for acute brain damage: cerebrospinal fluid levels correlate with severity of ischemic neurodegeneration in the rat. J Cereb Blood Flow Metab 25:1433–1444
Siman R, Roberts VL, McNeil E, Dang A, Bavaria JE, Ramchandren S, McGarvey M (2008) Biomarker evidence for mild central nervous system injury after surgically-induced circulation arrest. Brain Res 1213:1–11
Siman R, Toraskar N, Dang A, McNeil E, McGarvey M, Plaum J, Maloney E, Grady MS (2009) A panel of neuron-enriched proteins as markers for traumatic brain injury in humans. J Neurotrauma 26:1867–1877
Skouen JS, Brisby H, Otani K, Olmarker K, Rosengren L, Rydevik B (1991) Protein markers in cerebrospinal fluid in experimental nerve root injury. A study of slow-onset chronic compression effects or the biochemical effects of nucleus pulposus on sacral nerve roots. Spine (Phila Pa 1976) 24:2195–2200
Sloan TB, Jameson LC (2007) Electrophysiologic monitoring during surgery to repair the thoraco-abdominal aorta. J Clin Neurophysiol 24:316–327
St Rammos K, Koullias GJ, Hassan MO, Argyrakis NP, Voucharas CG, Scarupa SJ, Cowte TG (2002) Low preoperative HSP70 atrial myocardial levels correlate significantly with high incidence of postoperative atrial fibrillation after cardiac surgery. Cardiovasc Surg 10:228–232
Stecker MM, Cheung AT, Pochettino A, Kent GP, Patterson T, Weiss SJ, Bavaria JE (2001) Deep hypothermic circulatory arrest: I. Effects of cooling on electroencephalogram and evoked potentials. Ann Thorac Surg 71:14–21
Steensberg A, Daalsgaard MK, Secher NH, Pedersen BK (2006) Cerebrospinal fluid IL-6, HSP72, and TNF-alpha in exercising humans. Brain Behav Immunol 20:585–589
Sullivan TM, Sundt TM III (2006) Complications of thoracic aortic endografts: spinal cord ischemia and stroke. J Vasc Surg 43:85A–88A
Svensson LG, Crawford ES, Hess KR, Coselli JS, Safi HJ (1993) Experience with 1509 patients undergoing thoracoabdominal aortic operations. J Vasc Surg 17:357–368
Szerafin T, Hoetzenecker K, Hacker S, Horvath A, Pollreisz A, Arpad P, Mangold A, Wliszczak T, Dworschak M, Seitelberger R, Wolner E, Ankersmit HJ (2008) Heat shock proteins 27, 60, 70, 90alpha, and 20S proteosome in on-pump versus off-pump coronary artery bypass graft patients. Ann Thorac Surg 85:80–87
Tavaria M, Gabriele T, Kola I, Anderson RL (1996) A hitchhiker’s guide to the human Hsp70 family. Cell Stress Chaperones 1:23–28
Theodorakis NG, Drujan D, De Maio A (1999) Thermotolerant cells show an attenuated expression of Hsp70 after heat shock. J Biol Chem 274:12081–12086
Tian B, Cohen-Karni T, Qing Q, Duan X, Xie P, Lieber CM (2010) Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes. Science 329:830–834
Udelsman R, Blake MJ, Holbrook NJ (1991) Molecular responses to surgical stress: specific and simultaneous heat shock protein induction in the adrenal cortex, aorta, and vena cava. Surgery 110:1125–1131
van Dongen EP, Schepens MA, Morshuis WJ, ter Beek HT, Aarts LP, de Boer A, Boezeman EH (2001) Thoracic and thoracoabdominal aortic aneurysm repair: use of evoked potential monitoring in 118 patients. J Vasc Surg 34:1035–1040
van Eden W, Wick G, Albani S, Cohen I (2010) Stress, heat shock proteins, and autoimmunity. How immune responses to heat shock proteins are to be used for the control of chronic inflammatory diseases. Ann NY Acad Sci 1113:217–237
Velazquez OC, Bavaria JE, Pochettino A, Carpenter JP (1999) Emergency repair of thoracoabdominal aortic aneurysms with immediate presentation. J Vasc Surg 30:996–1003
Vitorini S, Storti S, Andreani G, Giusti L, Murzi B, Furfori P, Baroni A, De Lucia V, Luisi VS, Clerico A (2007) Heat shock protein 70-1 gene expression in pediatric heart surgery using blood cardioplegia. Clin Chem Lab Med 45:244–248
von Oppell UO, Dunne TT, De Groot KM, Zilla P (1994) Spinal cord protection in the absence of collateral circulation: meta-analysis of mortality and paraplegia. J Card Surg 9:685–691
von Reyn CR, Spaethling JM, Mesfin MN, Ma M, Neumar RW, Smith DH, Siman R, Meaney DF (2009) Calpain mediates proteolysis of the voltage-gated sodium channel alpha-subunit. J Neurosci 29:10350–10356
Wada T, Yao H, Miyamoto T, Mukai S, Yamamura M (2001) Prevention and detection of spinal cord injury during thoracic and thoracoabdominal aortic repairs. Ann Thorac Surg 72:80–84
Wagstaff MJ, Collaco-Moraes Y, Smith J, de Belleroche JS, Coffin RS, Latchman DS (1999) Protection of neuronal cells from apoptosis by Hsp27 delivered with a herpes simplex virus-based vector. J Biol Chem 274:5061–5069
Wang S, Xu X, Gu L (2006) Changes in the expression of c-fos & heat shock protein genes & blood flow velocity in the brain of rats undergoing myocardial ischaemia/reperfusion. Indian J Med Res 123:131–138
Westerheide SD, Morimoto RI (2005) Heat shock response modulators as therapeutic tools for diseases of protein conformation. J Biol Chem 280:33097–33100
Whitham M, Fortes MB (2008) Heat shock protein 72: release and biological significance during exercise. Front Biosci 13:1328–1339
Wieten L, van der Zee R, Goedemans R, Sijtsma J, Serafini M, Lubsen NH, van Eden W, Broere F (2010) Hsp70 expression and induction as a readout for detection of immune modulatory components in food. Cell Stress Chaperones 15:25–37
Williams JH, Ireland HE (2008) Sensing danger–Hsp72 and HMGB1 as candidate signals. J Leukoc Biol 83:489–492
Winnerkvist A, Anderson RE, Hansson LO, Rosengren L, Estrera AE, Huynh TT, Porat EE, Safi HJ (2007) Multilevel somatosensory evoked potentials and cerebrospinal proteins: indicators of spinal cord injury in thoracoabdominal aortic aneurysm surgery. Eur J Cardiothorac Surg 31:637–642
Wu D, Han D, Stecki AJ (2010) Immunoassay on free-standing electrospun membranes. ACS Appl Mater Interfaces 2:252–258
Xie PY, Li YP, Chan CP, Cheung KY, Cautherly GW, Renneberg R (2010) A one-step immunotest for rapid detection of heart-type fatty acid-binding protein in patients with acute coronary syndromes. J Immunoassay Immunochem 31:24–32
Yanai H, Ban T, Wang Z, Choi MK, Kawamura T, Negishi H, Nakasato M, Lu Y, Hangai S, Koshiba R, Sabitsky D, Ronfani L, Akira S, Bianchi ME, Honda K, Tamura T, Kodama T, Taniguchi T (2009) HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature 462:99–103
Yang T, Hsu C, Liao W, Chuang JS (2007) Heat shock protein 70 expression in epilepsy suggests stress rather than protection. Acta Neuropathol Berl 115:219–230
Yoo JC, Hayman MJ (2010) Annexin II binds to SHP2 and this interaction is regulated by HSP70 levels. Biochem Biophys Res Commun 356:906–911
Zedler S, Faist E (2006) The impact of endogenous triggers on trauma-associated inflammation. Curr Opin Crit Care 12:595–601
Zhan X, Ander BP, Jickling G, Turner R, Stamova B, Xu H, Liu D, Davis RR, Sharp FR (2010) Brief focal cerebral ischemia that simulates transient ischemic attacks in humans regulates gene expression in peripheral blood. J Cereb Blood Flow Metab 30:110–118
Zhang Y, Pan T, Fang G, Ma D, Wang S (2009) Development of a solid-phase extraction-enzyme-linked immunosorbent assay for the determination of 17beta-19-nortestosterone levels in antifatigue functional foods. J Food Sci 74:T67–T74
Zhang X, Xu Z, Zhou L, Chen Y, He M, Cheng L, Hu FB, Tanguay RM, Wu T (2010) Plasma levels of Hsp70 and anti-Hsp70 antibody predict risk of acute coronary syndrome. Cell Stress & Chaperones 15(5):675–686
Zhou L, Zhu T, Ye X, Yang L, Wang B, Liang X, Lu L, Tsao Y-P, Chen S-L, Li J, Xiao X (2010) Long-term protection against papillomavirus E7-positive tumor by a single vaccination of adeno-associated virus vectors encoding a fusion protein of inactivated E7 of human papillomavirus 16/18 and heat shock protein 70. Hum Gene Ther 21:109–119
Zou N, Ao L, Cleveland JC, Yang X, Su X, Cai GY, Banerjee A, Fullerton DA, Meng X (2010) Critical role of extracellular heat shock cognate protein 70 in the myocardial inflammatory response and cardiac dysfunction after global ischemia-reperfusion. Am J Physiol Heart Circ Physiol 294:H2805–H2813
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hecker, J.G., McGarvey, M. Heat shock proteins as biomarkers for the rapid detection of brain and spinal cord ischemia: a review and comparison to other methods of detection in thoracic aneurysm repair. Cell Stress and Chaperones 16, 119–131 (2011). https://doi.org/10.1007/s12192-010-0224-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12192-010-0224-8