Thermal preconditioning protocols for cardiac cells were identified which produce elevated HSP70 levels while maintaining high cell viability. Bovine aortic endothelial cells were heated with a water bath at temperatures ranging from 44to50°C for periods of 1-30min. Thermal stimulation protocols were determined which induce HSP70 expression levels ranging from 2.3 to 3.6 times the control while maintaining cell viabilities greater than 90%. An Arrhenius injury model fit to the cell damage data yielded values of A=1.4×1066s1 and Ea=4.1×105Jmol. Knowledge of the injury parameters and HSP70 kinetics will enhance dosimetry guideline development for thermal stimulation of heat shock proteins expression in cardiac tissue.

1.
Gowda
,
A.
,
Yang
,
C. J.
,
Asimakis
,
G. K.
,
Ruef
,
J.
,
Rastegar
,
S.
,
Runge
,
M. S.
, and
Motamedi
,
M.
, 1998, “
Cardioprotection by Local Heating: Improved Myocardial Salvage After Ischemia and Reperfusion
,”
Ann. Thorac. Surg.
0003-4975,
65
(
5
), pp.
1241
1247
.
2.
Richard
,
V.
,
Kaeffer
,
N.
, and
Thuillez
,
C.
, 1996, “
Delayed Protection of the Ischemic Heart from Pathophysiology to Therapeutic Applications
,”
Fundam. Clin. Pharmacol.
0767-3981,
10
(
4
), pp.
409
415
.
3.
Patel
,
B. A.
,
Khaliq
,
J.
, and
Evans
,
J.
, 1995, “
Hypoxia Induces HSP70 Gene Expression in Human Hepatoma (HEP G2) Cells
,”
Biochem. Mol. Biol. Int.
1039-9712,
36
, pp.
907
912
.
4.
Kabakov
,
A. E.
, and
Gabai
,
V. L.
, 1997,
Heat Shock Proteins and Cytoprotection: Atp-Deprived Mammalian Cells
,
Springer-Verlag
, Heidelberg, Chap. 1.
5.
Kukreja
,
R. C.
,
et al.
, 1994, “
Oxidant Stress Increases Heat Shock Protein 70 mRNA in Isolated Perfused Rat Heart
,”
Am. J. Physiol.
0002-9513,
267
(
6
), pp.
H2213
H2219
.
6.
Yang
,
X. M.
,
Baxter
,
G. F.
,
Heads
,
R. J.
,
Yellon
,
D. M.
,
Downey
,
J. M.
, and
Cohen
,
M. V.
, 1996, “
Infarct Limitation of the Second Window of Protection in a Conscious Rabbit Model
,”
Cardiovasc. Res.
0008-6363,
31
(
5
), pp.
777
783
.
7.
Kiang
,
J. G.
, and
Tsokos
,
G. C.
, 1998, “
Heat Shock Protein 70kDa: Molecular Biology, Biochemistry, and Physiology
,”
Pharmacology
0031-7012,
80
(
2
) pp.
183
201
.
8.
Martin
,
J.
,
Horwich
,
A.
, and
Hartl
,
F. U.
, 1992, “
Prevention of Protein Denaturation under Heat Stress by the Chaperonin HSP60
,”
Science
0036-8075,
258
, pp.
995
958
.
9.
Weich
,
H.
,
Buchner
,
J.
,
Zimmermann
,
R.
, and
Jakob
,
U.
, 1992, “
HSP90 Chaperones Protein Folding In Vitro
,”
Nature (London)
0028-0836,
358
(
6382
), pp.
169
170
.
10.
Currie
,
R. W.
,
Karmazyn
,
M.
,
Kloc
,
M.
, and
Mailer
,
K.
, 1988, “
Heat Shock Response is Associated With Enhanced Post-Ischemic Ventricular Recovery
,”
Circ. Res.
0009-7330,
63
(
3
), pp.
543
549
.
11.
Kawana
,
K.
,
Miyamoto
,
Y.
,
Tanonaka
,
K.
,
Han-No
,
Y.
,
Yoshida
,
H.
,
Takahashi
,
M.
, and
Takeo
,
S.
, 2000, “
Cytoprotective Mechanism of Heat Shock Protein 70 Against Hypoxia/Reoxygenation Injury
,”
J. Mol. Cell. Cardiol.
0022-2828,
32
(
12
), pp.
2229
2237
.
12.
Yellon
,
D. M.
,
Pasini
,
E.
,
Cargnoni
,
A.
,
Marber
,
M. S.
,
Latchman
,
D. S.
, and
Ferrari
,
R.
, 1992, “
The Protective Role of Heat Stress in the Ischemic and Reperfused Rabbit Myocardium
,”
J. Mol. Cell. Cardiol.
0022-2828,
24
, pp.
895
907
.
13.
Currie
,
R. W.
,
Tanguay
,
R. M.
, and
Kingma
,
J. G.
, 1993, “
Heat-Shock Response and Limitation of Tissue Necrosis During Occlusion/Reperfusion in Rabbit Hearts
,”
Circulation
0009-7322,
87
(
3
), pp.
963
971
.
14.
Marber
,
M. S.
,
Latchman
,
D. S.
,
Walker
,
J. M.
, and
Yellon
,
D. M.
, 1993, “
Cardiac Stress Protein Elevation 24hrs After Brief Ischemia or Heat Stress is Associated With Resistance to Myocardial Infarction
,”
Circulation
0009-7322,
88
(
3
), pp.
1264
1272
.
15.
Kaeffer
,
N.
,
Richard
,
V.
, and
Thuillez
,
C.
, 1994, “
Heat Stress Protects Coronary Against Coronary Endothelial Dysfunction After Myocardial Ischemia and Reperfusion in Rats
,”
Circulation
0009-7322,
89
(
3
), pp.
1254
1261
.
16.
Donnelly
,
T. J.
,
Sievers
,
F. L.
,
Vissern
,
F. L.
,
Welch
,
W. J.
, and
Wolfe
,
C. L.
, 1992, “
Heat Shock Protein Induction in Rat Hearts: A Role for Improved Myocardial Salvage After Ischemia and Reperfusion?
Circulation
0009-7322,
85
(
2
), pp.
769
778
.
17.
Morimoto
,
R. I.
, and
Santoro
,
M. G.
, 1998, “
Stress-Inducible Responses and Heat Shock Proteins: New Pharmacologic Targets for Cryoprotection
,”
Nat. Biotechnol.
1087-0156,
16
(
9
), pp.
833
838
.
18.
Wang
,
S.
,
Diller
,
K. R.
, and
Aggarwal
,
S.
, 2003, “
Heat Shock Protein 70 Expression Kinetics
,”
ASME J. Biomech. Eng.
0148-0731,
125
(
6
), pp.
794
797
.
19.
Ito
,
H.
,
et al.
, 1999, “
Thermal Preconditioning Protects Rat Cardiac Muscle Cells from Doxorubicin-Induced Apoptosis
,”
Life Sci.
0024-3205,
64
(
9
), pp.
755
761
.
20.
Tekin
,
L.
,
Bhargava
,
P.
, and
Kukreja
,
R. C.
, 2001, ”
Whole Body Hyperthermia and Preconditioning of the Heart: Basic Concepts, Complexity, and Potential Mechanisms
,”
Int. J. Hyperthermia
0265-6736,
17
(
5
), pp.
439
455
.
21.
Joyeux
,
M.
,
Boumendjel
,
A.
,
Carroll
,
R.
,
Ribuot
,
C.
,
Godin
,
D.
, and
Yellon
,
D.
, 2000, “
SB203580, A Mitogen-Activated Protein Kinase Inhibitor, Abolishes Resistance to Myocardial Infarction Induced by Heat Stress
,”
Cardiovasc. Drugs Ther.
0920-3206,
14
(
3
), pp.
337
343
.
22.
Kukreja
,
R.
,
Qian
,
Y.
,
Okubo
,
S.
, and
Flaherty
,
E.
, 1999, “
Role of Protein Kinase C and 72kDa Heat Shock Protein in Ischemic Tolerance Following Heat Stress in the Rat Heart
,”
Mol. Cell. Biochem.
0300-8177,
195
(
1–2
), pp.
123
131
.
23.
Clerk
,
A.
,
Fuller
,
S.
,
Michael
,
A.
, and
Sugden
,
P.
, 1998, “
Stimulation of Stress-Regulated Mitogen-Activated Protein Kinases (Stress-Activated Protein Kinases/c-Jun N-Terminal Kinases and p38-Mitogen-Activated Protein Kinases) in Perfused Rat Hearts by Oxidative and Other Stresses
,”
J. Biol. Chem.
0021-9258,
273
(
2
), pp.
728
734
.
24.
Hoag
,
J. B.
,
Qian
,
Y. Z.
,
Nayeem
,
M. A.
,
D’Angelo
,
M.
,
Kukreja
,
R. C.
, 1997, “
ATP-Sensitive Potassium Channel Mediates Delayed Ischemic Protection by Heat Stress in Rabbit Heart
,”
Am. J. Physiol.
0002-9513,
273
(
5
), pp.
H2458
H2464
.
25.
Joyeux
,
M.
,
Baxter
,
G. F.
,
Thomas
,
D. L.
,
Ribuot
,
C.
, and
Yellon
,
D. M.
, 1997, “
Protein Kinase C is Involved in Resistance to Myocardial Infarction Induced by Heat Stress
,”
J. Mol. Cell. Cardiol.
0022-2828,
29
(
12
), pp.
3311
3319
.
26.
Tekin
,
D.
,
Xi
,
L.
,
Zhao
,
T.
,
Tejero-Taldo
,
M. I.
,
Atluri
,
S.
, and
Kukreja
,
R. C.
, 2001, “
Mitogen-Activated Protein Kinases Mediate Heat Shock-Induced Delayed Protection in Mouse Heart
,”
Am. J. Physiol.
0002-9513,
281
(
2
), pp.
H523
H532
.
27.
Dybdahl
,
B.
,
Wahba
,
A.
,
Lien
,
E.
,
Trude
,
H.
,
Flo
,
W.
,
Anders
,
Q.
,
Nilofer
,
S.
,
Olav
,
F. M.
,
Espevik
,
T.
, and
Sundan
,
A.
, 2002, “
Inflammatory Response after Open Heart Surgery Release of Heat-Shock Protein 70 and Signaling Through Toll-Like Receptor-4
,”
Circulation
0009-7322,
105
(
6
), pp.
685
690
.
28.
Lin
,
E.
,
Calvano
,
S. E.
, and
Lowry
,
S. F.
, 2000, “
Inflammatory Cytokines and Cell Response in Surgery
,”
Surgery (St. Louis)
0039-6060,
127
(
2
), pp.
117
126
.
29.
Sondermann
,
H.
,
et al.
, 2000, “
Characterization of a Receptor for Heat Shock Protein 70 on Macrophages and Monocytes
,”
Biol. Chem.
1431-6730,
381
(
12
), pp.
1165
1174
.
30.
Lamb
,
D. J.
,
El-Sankary
,
W. A.
,
Ferns
, and
Gordon
,
A.
, 2002, “
Molecular Mimicry in Atherosclerosis: A Role for Heat Shock Proteins Inimmunisation
,”
Arteriosclerosis (Dallas)
0276-5047,
167
(
2
), pp.
177
185
.
31.
Madamanchi
,
N. R.
,
Li
,
S.
,
Patterson
,
C.
, and
Rouge
,
M. S.
, 2001, “
Reactive Oxygen Species Regulate Heat Shock Protein 70 via the JAK/STAT Pathway
,”
Arterioscler., Thromb., Vasc. Biol.
1079-5642,
21
(
3
), pp.
321
330
.
32.
Xu
,
Q.
,
Schett
,
G.
,
Li
,
C.
,
Hu
,
Y.
, and
Wick
,
G.
, 2000, “
Mechanical Stress-Induced Heat Shock Protein 70 Expression in Vascular Smooth Muscle Cells is Regulated by Rac and Ras Small G Proteins but not Mitogen-Activated Protein Kinases
,”
Circ. Res.
0009-7330,
86
(
11
), pp.
1122
1128
.
33.
Currie
,
R. W.
,
Tanguay
,
R. M.
, and
Kingma
,
J. G.
, 1993, “
Heat Shock Response and Limitation of Tissue Necrosis During Occlusion/Reperfusion in Rabbit Hearts
,”
Circulation
0009-7322,
87
(
3
),
1048
1051
.
34.
Yan
,
L.
,
Christians
,
E. S.
,
Liu
,
L.
,
Xiao
,
X.
,
Sohal
,
R. S.
, and
Benjamin
,
I. J.
, 2002, “
Mouse Heat Shock Transcription Factor 1 Deficiency Alters Cardiac Redox Homeostasis and Increases Mitochondrial Oxidative Damage
,”
EMBO J.
0261-4189,
21
(
19
), pp.
5164
5172
.
35.
Pirkkala
,
L.
,
Alastalo
,
T. P.
,
Zuo
,
X.
,
Benjamin
,
I. J.
, and
Sistonen
,
L.
, 2000, “
Disruption of Heat Shock Factor 1 Reveals an Essential Role in the Ubiquitin Proteolytic Pathway
,”
Mol. Cell. Biol.
0270-7306,
20
(
8
), pp.
2670
2675
.
36.
Manalo
,
D. J.
,
Lin
,
Z.
, and
Liu
,
A. Y.
, 2002, “
Redox-Dependent Regulation of the Conformation and Function of Human Heat Shock Factor 1
,”
Biochemistry
0006-2960,
41
(
8
), pp.
2580
2588
.
37.
Marchler
,
G.
, and
Wu
,
C.
, 2001, “
Modulation of Drosophila Heat Shock Transcription Factor Activity by the Molecular Chaperone DROJ1
,”
EMBO J.
0261-4189,
20
(
3
), pp.
499
509
.
38.
Knowlton
,
A. A.
,
Grenier
,
M.
, and
Kirchhoff
,
S. R.
, 2000, “
Phosphorylation at Tyrosine–524 Influences Nuclear Accumulation of HSP72 with Heat Stress
,”
Am. J. Physiol.
0002-9513,
278
(
6
), pp.
H2143
21499
.
39.
Diller
,
K. R.
,
Valvano
,
J. W.
, and
Pearce
,
J. A.
, 2000, “
Bioheat Transfer
.” in:
CRC Handbook of Thermal Engineering
,
F.
Kreith
, ed.,
CRC Press
, Boca Raton, pp.
4114
4187
.
40.
Fenn
,
A. J.
,
Wolf
,
G. L.
, and
Fogle
,
R. M.
, 1999, “
An Adaptive Microwave Phased Array for Targeted Heating of Deep Tumors in Intact Breast: Animal Study Results
,”
Int. J. Hyperthermia
0265-6736,
15
(
1
), pp.
45
61
.
41.
Amrani
,
M.
,
et al.
, 1997, “
Relative Induction of Heat Shock Protein in Coronary Endothelial Cells and Cardiomyocytes: Implications for Myocardial Protection
,”
J. Thorac. Cardiovasc. Surg.
0022-5223,
115
, pp.
200
209
.
42.
Leger
,
J.
,
Smith
,
F. M.
, and
Currie
,
R. W.
, 2000, “
Confocal Microscopic Localization of Constituitive and Heat Shock-Induced Proteins HSP70 and HSP27 in the Rat Heart
,”
Circulation
0009-7322,
102
, pp.
1703
1709
.
43.
Diaz
,
S. H.
,
Nelson
,
J. S.
, and
Wong
,
B. J. F.
, 2003, “
Rate Process Analysis of Thermal Damage in Cartilage
,”
Phys. Med. Biol.
0031-9155,
48
(
1
), pp.
19
29
.
44.
Takata
,
A. N.
et al.
, 1974, “
Thermal Model of Laser Induced Eye Damage, Final Rept. USAF School of Aerospace Medicine, Brooks AFB TX
,” Contract No. F41609–74-C–0005,
IIT Research Institute
, Chicago, IL.
45.
Agah
,
R.
, 1988, “
Quantitative Characterization of Arterial Tissue Thermal Damage
,” MSE thesis, The University of Texas at Austin.
46.
Sanghvi
,
N. T.
,
Foster
,
R. S.
,
Bihrle
,
R.
,
Casey
,
R.
,
Uchida
,
T.
,
Phillips
,
M. H.
,
Syrus
,
J.
,
Zaitsev
,
A. V.
,
Marich
,
K. W.
, and
Fry
,
F. J.
, 1999, “
Noninvasive Surgery of Prostate Tissue by High Intensity Focused Ultrasound: An Updated Report
,”
Eur. J. Ultrasound
0929-8266,
9
(
1
), pp.
19
29
.
47.
Uchida
,
T.
,
Muramoto
,
M.
,
Kyunou
,
H.
,
Iwamura
,
M.
,
Egawa
,
S.
, and
Koshiba
,
K.
, 1998, “
Clinical Outcome of High-Intensity Focused Ultrasound for Treating Benign Prostatic Hyperplasia: Preliminary Report
,”
Urology
0090-4295,
52
(
1
), pp.
66
71
.
48.
Sanghvi
,
N. T.
,
Fry
,
F. J.
,
Bihrle
,
R.
,
Foster
,
R. S.
,
Phillips
,
M. H.
,
Syrus
,
J. S.
,
Zaitsev
,
A. V.
, and
Hennige
,
C. W.
, 1996, “
Noninvasive Surgery of Prostate Tissue by High-Intensity Focused Ultrasound
,”
IEEE Trans. Ultrason. Ferroelectr. Freq. Control
0885-3010,
43
(
6
), pp.
243
247
.
49.
Paiva
,
M.
,
Blackwell
,
K.
, and
Saxton
,
R.
, 2002, “
Nd–YAG Laser Therapy for Palliation of Recurrent Squamous Cell Carcinomas in the Oral Cavity
,”
Lasers Surg. Med.
0196-8092,
31
(
1
), pp.
64
69
.
50.
Dorr
,
L. N.
, and
Hynymen
,
K.
1993, “
The Effects of Tissue Heterogeneities and Large Blood Vessels on Thermal Exposure Induced by Short High-Power Ultrasound Pulses
,”
Int. J. Hyperthermia
0265-6736,
8
(
1
), pp.
45
59
.
51.
LaFon
,
C.
,
Prat
,
F.
,
Chapelon
,
J. Y.
,
Gorry
,
F.
,
Margomari
,
J.
,
Theillere
,
Y.
, and
Cathigno
,
I. D.
, 2000, “
Cylindrical Thermal Coagulation Necrosis using an Interstitial Applicator with a Plane Ultrasonic Transducer: In Vitro and In Vivo Experiments Versus Computer Simulations
,”
Int. J. Hyperthermia
0265-6736,
16
(
6
), pp.
508
522
.
52.
Goldberg
,
S. N.
,
Gazelle
,
G. S.
, and
Mueller
,
P. R.
, 2000, “
The Thermal Ablation Therapy for Focal Malignancy: A Unified Approach to Underlying Principles, Techniques, and Diagnostic Imaging Guidance
,”
AJR, Am. J. Roentgenol.
0361-803X,
174
(
3
), pp.
323
331
.
You do not currently have access to this content.