title: 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.
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.
authors.affiliation: Department of Anesthesiology and Critical Care, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104-6112, USA. heckerj@uphs.upenn.edu
authors.forename: James G
authors.initials: JG
authors.lastname: Hecker
authors.forename: Michael
authors.initials: M
authors.lastname: McGarvey
mesh_terms: D017545:Aortic Aneurysm, Thoracic / Q000175:diagnosis*; D015415:Biomarkers / Q000032:analysis; D002545:Brain Ischemia / Q000175:diagnosis*; D006360:Heat-Shock Proteins / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry; D006801:Humans; D020760:Spinal Cord Ischemia / Q000175:diagnosis*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D006360:Heat-Shock Proteins
references.citation: J Cardiovasc Surg (Torino). 2007 Apr;48(2):233-7
references.pmid: 17410072
references.citation: Cell Stress Chaperones. 2010 Jan;15(1):25-37
references.pmid: 19472075
references.citation: Brain Res. 2008 Jun 5;1213:1-11
references.pmid: 18456245
references.citation: Int J Hyperthermia. 2005 Aug;21(5):393-402
references.pmid: 16048837
references.citation: J Neurotrauma. 2009 Nov;26(11):1867-77
references.pmid: 19811094
references.citation: Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2126-30
references.pmid: 7892235
references.citation: Ann Thorac Surg. 2002 Aug;74(2):413-9; discussion 420-1
references.pmid: 12173822
references.citation: Ann Thorac Surg. 1985 Jan;39(1):37-46
references.pmid: 3966835
references.citation: J Vasc Surg. 2002 Apr;35(4):631-9
references.pmid: 11932655
references.citation: J Biosci. 2007 Apr;32(3):579-84
references.pmid: 17536177
references.citation: J Vasc Surg. 2006 Feb;43(2):217-22; discussion 223
references.pmid: 16476589
references.citation: Int J Exp Pathol. 2008 Jun;89(3):209-15
references.pmid: 18460073
references.citation: Eur J Cardiothorac Surg. 2007 Apr;31(4):637-42
references.pmid: 17306553
references.citation: J Clin Invest. 2005 Oct;115(10):2633-9
references.pmid: 16200196
references.citation: Neurobiol Dis. 2004 Jul;16(2):311-20
references.pmid: 15193288
references.citation: J Neurosurg Anesthesiol. 2010 Jan;22(1):46-52
references.pmid: 19996767
references.citation: Ann Neurol. 2000 Nov;48(5):809-12
references.pmid: 11079549
references.citation: J Biol Chem. 2005 Jun 17;280(24):23349-55
references.pmid: 15826944
references.citation: J Clin Invest. 1995 Jan;95(1):3-12
references.pmid: 7814629
references.citation: Semin Thorac Cardiovasc Surg. 1998 Jan;10(1):29-34
references.pmid: 9469775
references.citation: Brain Pathol. 1994 Jan;4(1):67-76
references.pmid: 8025704
references.citation: Zhonghua Er Ke Za Zhi. 2004 Jun;42(6):441-5
references.pmid: 15265432
references.citation: Ann Neurol. 2000 Nov;48(5):795-8
references.pmid: 11079545
references.citation: Brain Res Bull. 2003 Aug 15;61(3):265-79
references.pmid: 12909297
references.citation: Eur J Obstet Gynecol Reprod Biol. 2008 Aug;139(2):133-8
references.pmid: 18249485
references.citation: J Neurosurg Anesthesiol. 2009 Oct;21(4):302-6
references.pmid: 19955892
references.citation: J Immunol. 2005 Sep 1;175(5):2900-12
references.pmid: 16116176
references.citation: Cell Stress Chaperones. 2008 Dec;13(4):435-46
references.pmid: 18418731
references.citation: Am J Physiol Regul Integr Comp Physiol. 2009 Mar;296(3):R575-86
references.pmid: 19158413
references.citation: Semin Thorac Cardiovasc Surg. 1998 Jan;10(1):35-9
references.pmid: 9469776
references.citation: Glia. 2002 Sep;39(3):279-91
references.pmid: 12203394
references.citation: Anesthesiology. 2008 Apr;108(4):580-7
references.pmid: 18362588
references.citation: Minerva Chir. 2006 Dec;61(6):483-91
references.pmid: 17211353
references.citation: Ann Thorac Surg. 2005 Mar;79(3):865-71; discussion 871
references.pmid: 15734396
references.citation: Diabetes. 2008 Jul;57(7):1966-70
references.pmid: 18390793
references.citation: FEBS Lett. 2001 Nov 9;508(1):36-8
references.pmid: 11707263
references.citation: Methods. 2007 Nov;43(3):168-75
references.pmid: 17920512
references.citation: Ann Vasc Surg. 2002 Jul;16(4):436-41
references.pmid: 12089629
references.citation: Am J Physiol Heart Circ Physiol. 2008 Jun;294(6):H2805-13
references.pmid: 18441202
references.citation: Cell Stress Chaperones. 1999 Dec;4(4):205-10
references.pmid: 10590834
references.citation: BMC Cancer. 2009 Oct 06;9:353
references.pmid: 19807914
references.citation: Analyst. 2010 Jun;135(6):1345-50
references.pmid: 20358056
references.citation: Acta Neuropathol. 2008 Feb;115(2):219-30
references.pmid: 17929041
references.citation: Cell Stress Chaperones. 1999 Dec;4(4):223-34
references.pmid: 10590836
references.citation: Neurosurgery. 2001 Jun;48(6):1255-8; discussion 1258-60
references.pmid: 11383727
references.citation: Circulation. 2006 Dec 12;114(24):2611-8
references.pmid: 17145990
references.citation: Anesthesiology. 2009 Oct;111(4):844-54
references.pmid: 19741499
references.citation: J Food Sci. 2009 Oct;74(8):T67-74
references.pmid: 19799684
references.citation: Clin Chem Lab Med. 2007;45(2):244-8
references.pmid: 17311516
references.citation: Exp Physiol. 2004 May;89(3):271-7
references.pmid: 15123562
references.citation: Surgery. 1982 Dec;92(6):1103-8
references.pmid: 7147188
references.citation: Curr Opin Crit Care. 2006 Dec;12(6):595-601
references.pmid: 17077693
references.citation: Mol Cell Biol. 2003 Nov;23(21):7628-37
references.pmid: 14560008
references.citation: J Vasc Surg. 2003 Jun;37(6):1169-74
references.pmid: 12764260
references.citation: J Vasc Surg. 1999 Dec;30(6):996-1003
references.pmid: 10587383
references.citation: J Anesth. 2006;20(4):314-8
references.pmid: 17072699
references.citation: Cell Stress Chaperones. 2010 May;15(3):237-47
references.pmid: 19821156
references.citation: Ann Thorac Surg. 2008 Jan;85(1):80-7
references.pmid: 18154785
references.citation: Physiol Res. 2005;54(3):349-56
references.pmid: 15974836
references.citation: J Vasc Surg. 2006 Feb;43(2):239-46
references.pmid: 16476594
references.citation: Spinal Cord. 2009 Jul;47(7):519-25
references.pmid: 19153591
references.citation: Br J Surg. 2002 Apr;89(4):442-5
references.pmid: 11952585
references.citation: Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9873-7
references.pmid: 1658790
references.citation: Exp Neurol. 2004 Jan;185(1):81-96
references.pmid: 14697320
references.citation: J Neurosci. 2008 Mar 5;28(10):2320-31
references.pmid: 18322079
references.citation: J Matern Fetal Neonatal Med. 2008 Jul;21(7):449-61
references.pmid: 18570125
references.citation: J Leukoc Biol. 2008 Mar;83(3):489-92
references.pmid: 18156188
references.citation: Cell Stress Chaperones. 2009 Jan;14(1):105-11
references.pmid: 18663603
references.citation: Lab Chip. 2010 Apr 7;10(7):843-51
references.pmid: 20300670
references.citation: Brain Res Dev Brain Res. 1994 Jan 14;77(1):111-21
references.pmid: 8131258
references.citation: J Clin Neurophysiol. 2007 Aug;24(4):336-43
references.pmid: 17938602
references.citation: Hum Gene Ther. 2010 Jan;21(1):109-19
references.pmid: 19715402
references.citation: Brain Res Mol Brain Res. 1997 Aug;48(1):87-96
references.pmid: 9379854
references.citation: J Vasc Surg. 2002 Apr;35(4):640-7
references.pmid: 11932656
references.citation: Ann Thorac Surg. 1999 Jun;67(6):1943-6; discussion 1953-8
references.pmid: 10391345
references.citation: Inflamm Allergy Drug Targets. 2007 Jun;6(2):91-100
references.pmid: 17692032
references.citation: Trends Biochem Sci. 2008 Feb;33(2):71-9
references.pmid: 18182297
references.citation: ACS Appl Mater Interfaces. 2010 Jan;2(1):252-8
references.pmid: 20356242
references.citation: Cardiovasc Surg. 2002 Jun;10(3):228-32
references.pmid: 12044430
references.citation: J Reprod Immunol. 2008 Oct;79(1):12-7
references.pmid: 18715652
references.citation: Exp Neurol. 2004 Jan;185(1):97-108
references.pmid: 14697321
references.citation: Front Biosci. 2008 Jan 01;13:1328-39
references.pmid: 17981633
references.citation: Cell Stress Chaperones. 2009 Mar;14(2):151-9
references.pmid: 18686014
references.citation: Surgery. 1991 Dec;110(6):1125-31
references.pmid: 1660628
references.citation: FEBS Lett. 2007 Jul 31;581(19):3702-10
references.pmid: 17544402
references.citation: Cell Stress Chaperones. 2004 Autumn;9(3):276-80
references.pmid: 15544165
references.citation: Neurology. 2004 May 11;62(9):1634-6
references.pmid: 15136701
references.citation: J Vasc Surg. 1993 Feb;17(2):357-68; discussion 368-70
references.pmid: 8433431
references.citation: Ann Thorac Surg. 2007 Feb;83(2):456-61
references.pmid: 17257969
references.citation: Ann Thorac Surg. 1997 Oct;64(4):999-1003
references.pmid: 9354517
references.citation: J Vasc Surg. 2001 Dec;34(6):1035-40
references.pmid: 11743557
references.citation: J Cereb Blood Flow Metab. 2010 Jan;30(1):92-101
references.pmid: 19724284
references.citation: J Neurosci. 2009 Aug 19;29(33):10350-6
references.pmid: 19692609
references.citation: J Vasc Surg. 1999 Aug;30(2):219-28
references.pmid: 10436441
references.citation: Anesth Analg. 2010 Jan 1;110(1):174-80
references.pmid: 19897802
references.citation: J Innate Immun. 2010;2(3):238-47
references.pmid: 20375559
references.citation: Neurosci Lett. 2008 May 9;436(2):223-6
references.pmid: 18394800
references.citation: Experientia. 1994 Nov 30;50(11-12):979-86
references.pmid: 7988673
references.citation: Spine (Phila Pa 1976). 1999 Nov 1;24(21):2195-200
references.pmid: 10562983
references.citation: J Biol Chem. 1999 Apr 23;274(17):12081-6
references.pmid: 10207033
references.citation: Ann Surg. 2002 Oct;236(4):471-9; discussion 479
references.pmid: 12368676
references.citation: J Cereb Blood Flow Metab. 2005 Nov;25(11):1433-44
references.pmid: 15902199
references.citation: J Neurotrauma. 2005 Sep;22(9):966-77
references.pmid: 16156712
references.citation: Trends Neurosci. 1999 Mar;22(3):97-9
references.pmid: 10199631
references.citation: J Vasc Surg. 2006 Feb;43 Suppl A:85A-88A
references.pmid: 16473178
references.citation: Eur J Cardiothorac Surg. 2004 Jun;25(6):985-92
references.pmid: 15144999
references.citation: J Vasc Surg. 1986 Mar;3(3):389-404
references.pmid: 3951025
references.citation: Nature. 2009 Nov 5;462(7269):99-103
references.pmid: 19890330
references.citation: Eur J Biochem. 1995 Jul 15;231(2):454-65
references.pmid: 7635158
references.citation: Eur J Cardiothorac Surg. 2002 Sep;22(3):415-20
references.pmid: 12204733
references.citation: Cell Stress Chaperones. 1996 Apr;1(1):23-8
references.pmid: 9222585
references.citation: Indian J Med Res. 2006 Feb;123(2):131-8
references.pmid: 16575111
references.citation: Cochrane Database Syst Rev. 2004;(1):CD003635
references.pmid: 14974026
references.citation: Anal Chem. 2010 May 1;82(9):3803-11
references.pmid: 20353191
references.citation: J Card Surg. 1994 Nov;9(6):685-91
references.pmid: 7841649
references.citation: J Immunoassay Immunochem. 2010;31(1):24-32
references.pmid: 20391015
references.citation: J Clin Neurophysiol. 2007 Aug;24(4):316-27
references.pmid: 17938600
references.citation: Cell Stress Chaperones. 2009 Mar;14(2):117-31
references.pmid: 18668350
references.citation: Methods. 2007 Nov;43(3):229-37
references.pmid: 17920520
references.citation: J Thorac Cardiovasc Surg. 1981 May;81(5):669-74
references.pmid: 7218830
references.citation: Brain Behav Immun. 2006 Nov;20(6):585-9
references.pmid: 16647242
references.citation: Anesthesiol Clin North Am. 2001 Dec;19(4):923-45
references.pmid: 11778387
references.citation: Am J Surg. 1998 Aug;176(2):92-101
references.pmid: 9737610
references.citation: Sci China C Life Sci. 2004 Apr;47(2):107-14
references.pmid: 15379242
references.citation: Ann Thorac Surg. 1999 Jun;67(6):1937-9; discussion 1953-8
references.pmid: 10391343
references.citation: Circulation. 2009 Dec 22;120(25):2519-28
references.pmid: 19996018
references.citation: Ann Thorac Surg. 2001 Jan;71(1):14-21
references.pmid: 11216734
references.citation: Shock. 2006 Jul;26(1):20-4
references.pmid: 16783193
references.citation: Clin Vaccine Immunol. 2010 Jun;17(6):904-9
references.pmid: 20392886
references.citation: Cancer Sci. 2009 Oct;100(10):1870-9
references.pmid: 19659607
references.citation: Heart. 2005 Sep;91(9):1148-53
references.pmid: 16103543
references.citation: J Vasc Surg. 2002 Jan;35(1):30-7
references.pmid: 11802130
references.citation: Ann Thorac Surg. 2001 Jul;72(1):80-4; discussion 85
references.pmid: 11465235
references.citation: J Trauma. 2002 Apr;52(4):611-7; discussion 617
references.pmid: 11956372
references.citation: Biochem Biophys Res Commun. 2007 May 18;356(4):906-11
references.pmid: 17395158
references.citation: Eur Spine J. 2007 Jun;16(6):787-93
references.pmid: 16804674
references.citation: Can J Vet Res. 2010 Jan;74(1):71-4
references.pmid: 20357963
references.citation: Neurocrit Care. 2008;9(3):344-51
references.pmid: 18483880
references.citation: Immunogenetics. 1990;32(4):242-51
references.pmid: 1700760
references.citation: Br J Anaesth. 2009 Jul;103(1):89-98
references.pmid: 19502287
references.citation: Handb Exp Pharmacol. 2008;(183):111-27
references.pmid: 18071657
references.citation: Science. 2010 Aug 13;329(5993):830-4
references.pmid: 20705858
references.citation: Exerc Immunol Rev. 2005;11:46-52
references.pmid: 16385843
references.citation: J Cell Physiol. 1989 Feb;138(2):257-66
references.pmid: 2918030
references.citation: Ann Thorac Surg. 1999 Jun;67(6):1947-52; discussion 1953-8
references.pmid: 10391346
references.citation: Neurosci Lett. 2007 Mar 19;415(1):77-80
references.pmid: 17240064
references.citation: J Cereb Blood Flow Metab. 2010 Jan;30(1):110-8
references.pmid: 19738631
references.citation: J Biol Chem. 2005 Sep 30;280(39):33097-100
references.pmid: 16076838
references.citation: Brain Res Mol Brain Res. 2005 Apr 4;134(2):256-74
references.pmid: 15836922
references.citation: J Biol Chem. 1999 Feb 19;274(8):5061-9
references.pmid: 9988753
references.citation: Exp Neurol. 2008 Aug;212(2):275-84
references.pmid: 18511046
references.citation: J Vasc Surg. 2004 Jul;40(1):36-44
references.pmid: 15218460
references.citation: Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010 May-Jun;2(3):291-304
references.pmid: 20336708
references.citation: Cardiovasc Surg. 2002 Aug;10(4):434-41
references.pmid: 12359421
references.citation: Ann Thorac Surg. 2002 Nov;74(5):S1873-6; discussion S1892-8
references.pmid: 12440684
references.citation: Cell Stress Chaperones. 2010 Sep;15(5):675-86
references.pmid: 20300983
references.citation: Ann N Y Acad Sci. 2007 Oct;1113:217-37
references.pmid: 17584980