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Cardiovascular Research 2002 55(2):341-348; doi:10.1016/S0008-6363(02)00404-2
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Copyright © 2002, European Society of Cardiology

Increased preload directly induces the activation of heat shock transcription factor 1 in the left ventricular overloaded heart

Junichiro Nishizawaa,b,*, Akira Nakaib,1, Masashi Komedaa, Toshihiko Bana,2 and Kazuhiro Nagatab,c

aDepartment of Cardiovascular Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan
bDepartment of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
cCREST (Core Research for Evolutional Science and Technology), JST (Japanese Science and Technology Cooperation), Japan

nishizaw{at}kcn.ne.jp

* Corresponding author. Current address: Department of Cardiovascular Surgery, Tenri Hospital, 200 Mishima, Tenri, Nara, 632-8552 Japan. Tel.: +81-743-635-611; fax: +81-743-625-576

Received 9 October 2001; accepted 7 March 2002


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Objectives: The rapid induction of heat shock proteins (HSPs) by cardiac overload has been shown using in vivo models and it is assumed that HSPs are involved in myocardial protection against cardiac overload. However, the mechanisms for the induction of heat shock response by cardiac overload remain unclear. We examined whether increased preload as mechanical stress directly induces heat shock gene expression. Methods: Rat hearts were isolated and perfused with Krebs–Henseleit buffer by the Langendorff method. Whole-cell extracts were prepared for gel mobility shift assay using oligonucleotides containing the heat shock element. We examined the induction of the DNA-binding activity of heat shock transcription factor (HSF), by which the transcription of heat shock genes is mainly regulated, during increased preload of left ventricle (LV) or perfusion with the buffer containing epinephrine, norepinephrine, angiotensin II, or vasopressin. Results: In preloaded hearts, with LVEDP of both 30 and 50 mmHg, the DNA-binding activity of HSF1 was detected at 10 min, and increased at 20 and 60 min. At any time point, the activity with LVEDP of 50 mmHg was stronger than that with LVEDP of 30 mmHg. However, none of these hypertensive agents activated the DNA-binding activities of HSF. In afterloaded hearts, with the perfusion of norepinephrine, the activation of HSF was not induced. Conclusion: Our findings demonstrate that increased preload as mechanical stress directly induces the activation of HSF1 in the LV-overloaded heart.

KEYWORDS Gene expression; Mechanotransduction; Sequence (DNA/RNA/prot); Ventricular function


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
In the overloaded myocardium, mechanical stress is considered to be the trigger inducing a growth response resulting in cardiac hypertrophy, which is initially beneficial to overload adaptation [1]. However, the adaptation has its limits and heart failure as a final form of hypertrophy causes arrhythmia and relative myocardial ischemia, which increases the risk of sudden death [2]. There have been a lot of studies on the mechanisms of hypertrophic growth, but much still remains to be investigated [1,2].

The induction of heat shock proteins (HSPs) in the heart has been observed under various physiological stresses including ischemia and hyperthermia [3–8]. The rapid induction of HSPs by cardiac overload similarly has been shown using in vivo models [5,9–11]. In addition, HSPs were demonstrated to have a role in myocardial protection, as well as cytoprotection or repair, of organisms under various physiological stresses [8,12–17]. Thus, it seems reasonable to suppose that heat shock proteins play an important role in myocardial protection against cardiac overload. However, an in vitro study showed a lack of stretch-induced expression of HSP 70 mRNA in cultured cardiac myocytes [18]. Factors other than mechanical stress, such as catecholamine or hypertensive agents, that are released from organs other than the heart may cause the induction of heat shock proteins.

In the present study, therefore, we sought to determine whether mechanical stress directly induces heat shock gene expression. Heat shock gene regulation is mainly mediated at the transcriptional level by the activation of a pre-existing transcription activator, the heat shock transcription factor (HSF). HSF binds to heat shock element (HSE), which is present upstream of all heat shock genes and induces heat shock gene transcription (for a review, see Ref. [8]). In vertebrate cells, a family of HSF has been identified, and functional differences exist among the members of this family [19–23]. Under stress conditions, HSF1 induces heat shock gene transcription through acquisition of the DNA-binding activity [24,25]. We examined the induction of the DNA binding activity of HSF1 by gel mobility shift assay during increased preload of left ventricle (LV) or perfusion of hypertensive agents released in heart failure or hypotension.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1 Isolated heart perfusion
Male Sprague–Dawley rats (250 to 300 g), obtained from Shimizu Laboratory Supplies, were anesthetized with diethyl ether and administered heparin (200 IU i.v.). The hearts were excised and then perfused, as described previously [7,26], by the Langendorff method with Krebs–Henseleit buffer (consisting of, in mmol/l: NaCl 118, NaHCO3 25, KCl 4.6, MgSO4 1.2, KH2PO4 1.2, CaCl2 2.5 and glucose 11) at 37 °C at constant pressure of 100 cm H2O. The perfusate was bubbled with 95% O2–5% CO2 gas, and the pH of the buffer was 7.4. The temperature of the perfusion buffer measured at the aortic cannula was maintained at 37 °C (or 42 °C during the heat shock period), and the hearts were contained in a water-jacketed chamber at the same temperature. The LV pressure and LV dP/dt were monitored through the use of a fluid-filled latex balloon inserted into the LV via the left atrium and connected to a pressure transducer. The balloon volume was adjusted to obtain an LV end-diastolic pressure (LVEDP) of 5 to 9 mmHg. The LV developed pressure (LVDP) was calculated as the difference between the peak systolic and end-diastolic pressures. Coronary flow was measured by timed collection of the overflow from the hearts. The creatine kinase (CK) concentration was determined according to the spectrophotometric method of Rosalki (see [7,26]).

The investigation conforms with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996).

2.2 Experimental protocols
The experimental protocols are summarized in Fig. 1. In all hearts, after a 30-min stabilization, baseline hemodynamic measurements were made. Then, in the heat shock experiments, warm (42 °C) buffer was perfused for 20 min.


Figure 1
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  		Fig. 1 Experimental protocols. The isolated rat hearts were rapidly excised, mounted on a Langendorff perfusion apparatus and perfused with Krebs–Henseleit buffer at constant pressure of 100 cm H2O. In the heat-shocked group, after a 30-min stabilization period (37 °C), the temperature of the perfusion buffer and the heating jacket was raised to 42 °C for 20 min. In the ischemia/reperfusion experiments, after stabilization, the hearts were subjected to 20-min global ischemia by clamping of the aortic cannula, with 10-min reperfusion (Rep) thereafter. In the experiments on LV overload, after stabilization, LVEDP was set and maintained at 30 or 50 mmHg for the indicated time periods by adjusting the LV balloon volume. In the experiments on the effects of catecholamine or hypertensive agents, after stabilization, the perfusate was substituted with the buffer containing epinephrine (1.0 µmol/l), norepinephrine (1.0 µmol/l), angiotensin II (10 nmol/l) or vasopressin (1.0 nmol/l) for 10 or 60 min. After stabilization, the control hearts were perfused for 60 min under the same conditions as during stabilization.

 
In the ischemia/reperfusion experiments, isolated hearts were subjected to 20-min global ischemia by clamping the aortic cannula followed by 10-min reperfusion. Throughout the ischemic period only, the intraventricular balloon was kept deflated. Postischemic reperfusion was applied under the same conditions as during stabilization.

In the experiments on LV overload, after a 30-min stabilization, LVEDP was set and maintained at 30 or 50 mmHg for the indicated time period by adjusting the LV balloon volume [27].

In the experiments on the effects of catecholamine or hypertensive agents, the perfusate was substituted after a stabilization with the buffer containing epinephrine (1.0 µmol/l), norepinephrine (1.0 µmol/l), angiotensin II (10 nmol/l) or vasopressin (1.0 nmol/l) for 10 or 60 min.

Control hearts were perfused under the same conditions as during stabilization for 60 min after 30-min stabilization. Measurements of hemodynamic parameters and CK efflux were made at the baseline and in the 10th minute of LV overload or perfusion of hypertensive agents. Hearts that developed ventricular fibrillation and did not return to normal sinus rhythm were excluded from the data analysis. At the end of each experiment, the ventricular tissue was quickly frozen in liquid nitrogen and then stored at –80 °C.

2.3 Preparation of cell extracts
For preparation of whole-cell extracts from the hearts, the frozen samples were crushed and homogenized with a Polytron homogenizer (Kinematica) in high-salt buffer as described previously [7,26]. The lysates were kept on ice for 5 min and then centrifuged at 100,000 g for 5 min at 4 °C. The supernatants were frozen in liquid nitrogen and stored at –80 °C.

2.4 Gel mobility shift assay
Whole-cell extracts from the hearts were assayed by gel mobility shift assay as described previously [7,22,26], using a double-stranded synthetic HSE. Binding reactions with protein extracts (40 µg) were performed for 20 min at 25 °C in 25 µl of the binding buffer containing 0.2 ng of 32P-labeled probe and 0.5 µg of poly(dI-dC)·poly(dI-dC) (Pharmacia Biotech). The samples were then electrophoresed on a nondenaturing 4% polyacrylamide gel, dried, and autoradiographed. For antibody supershift experiments, 2.0 µl of diluted (1:10 with phosphate-buffered saline, PBS) specific antisera raised against recombinant chicken HSF1 ({alpha}HSF1β) or HSF2 ({alpha}HSF2{delta}) were added to whole-cell extracts before the binding reaction [7,26]. For the competition experiments, the binding reaction mixtures contained a 50-fold molar excess of unlabeled HSE oligonucleotides.

2.5 Statistical analysis
All values are expressed as mean±S.E.M. Statistical comparisons between the baseline and 10 min of LV overload or perfusion with the hypertensive agents in the hemodynamic study were assessed for significance with the paired t test. Comparisons were made between hearts subjected to LV overload or perfused with drugs and controlled hearts at individual time points using the unpaired t test. Statistical significance was defined as P<0.05.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
The changes in hemodynamic parameters and CK efflux before or 10 min after LV overload or perfusion with hypertensive agents are summarized in Table 1.


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  		Table 1 Hemodynamic changes due to LV overload or hypertensive agents

 
In the LV overload groups, LVEDP was significantly higher than any other groups because LVEDP was set and maintained at 30 or 50 mmHg by adjusting the LV balloon volume. The LVDP of the LVEDP 50 mmHg group was significantly lower compared with that of the control group.

In the epinephrine-perfused group, there was no significant difference, but there was a trend toward a higher heart rate and LV dP/dt compared with the control group. In the norepinephrine-perfused group, the heart rate, LVDP, LV dP/dt and CK efflux were significantly higher compared with those of the control group. In the angiotensin II-perfused group, the coronary flow was lower compared with that of the control group. In the vasopressin-perfused group, the coronary flow, LVDP and LV dP/dt were lower compared with the control group. In all groups, there were no significant differences between baseline data.

The changes in hemodynamic parameters and CK efflux during 42 °C heat shock or reperfusion after 20-min ischemia are also summarized in Table 2, showing no significant differences between baseline data.


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  		Table 2 Hemodynamic changes during 42 °C heat shock or reperfusion after 20-min ischemia

 
All of the experiments were repeated using at least three rats, and representative data of reproducible results are shown.

3.1 Activation of HSF by LV overload
It has been demonstrated that the HSE-binding activity of HSF is induced by heat shock or ischemia/reperfusion. We investigated the effect of LV overload on HSF activation. The HSE-binding activities of HSF in hearts overloaded by LVEDP of 30 or 50 mmHg were examined by gel mobility shift assays using an end-labeled HSE oligonucleotide as a probe (Fig. 2). No HSE-binding activity was observed in control hearts (lane 1), whereas significant binding activity was induced by LV overload (lanes 4–6, 8–10) as well as by heat shock (lane 2). In hearts overloaded with LVEDP of both 30 and 50 mmHg, the activity was detected at 10 min (lanes 4 and 8) and increased at 20 (lanes 5 and 9) and 60 min (lanes 6 and 10), while that of 20 min was almost equal to that of 60 min. At any time point, the activity with LVEDP of 50 mmHg was stronger than that with LVEDP of 30 mmHg, while the activity with LVEDP of 50 or 30 mmHg was weaker than that with heat shock at 42 °C for 20 min. Competition with an excess of unlabeled HSE oligonucleotide eliminated protein binding to the labeled probe (lanes 7 and 11).


Figure 2
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  		Fig. 2 HSE-binding activity of HSF during LV overload. In the LV overload group, LV end-diastolic pressure (LVEDP) was set and maintained at 30 or 50 mmHg as indicated, by adjusting the LV balloon volume for the indicated time periods after 30-min stabilization. Control hearts (C) were perfused with the buffer for 90 min. Heat-shocked hearts (HS) were perfused with 42 °C buffer for 20 min after stabilization. Whole cell extracts from hearts (40 µg/lane) were analyzed by gel mobility shift assay using a radiolabeled HSE oligonucleotide. Competition assays of hearts submitted to heat shock or LV overload were also performed with binding reaction mixtures containing 50-fold excesses of unlabeled HSE oligonucleotides (lanes 3, 7 and 11). Free indicates free probe.

 
3.2 Specific activation of HSF1
It has been shown that HSF1 acquires DNA-binding activity in response to chemical and physiological stresses such as elevated temperature, ischemia/reperfusion, oxidative stress, and exposure to heavy metals and amino acid analogues. To ascertain whether HSF1 was responsible for the activity induced by LV overload, we used antisera against HSF1 and HSF2 to retard the electrophoretic mobility of HSF–HSE complexes. In extracts of hearts overloaded with LVEDP 30 mmHg for 60 min, as well as those of hearts submitted to 20-min ischemia followed by 10-min reperfusion, supershifts or decreases in mobility of the complex were observed when antiserum against HSF1 was used (Fig. 3, lane 6), although anti-HSF2 antiserum had no effect (Fig. 3, lane 7). These results demonstrate that HSF1 is the primary component of HSE-binding activity induced by LV overload, as well as by other chemical or physiological stresses.


Figure 3
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  		Fig. 3 Antibody recognition of HSF in hearts exposed to ischemia/reperfusion or LV overload. Whole cell extracts were prepared from hearts submitted to 20-min ischemia and 10-min reperfusion (Isch 20+Rep 10), or LV overload by setting LVEDP at 30 mmHg for 60 min. Cell extracts (40 µg/lane) were incubated with anti-HSF1 (lanes 3 and 6) or anti-HSF2 (lanes 4 and 7) antiserum before the DNA binding reaction, and gel mobility shift assay was performed. Cell extracts without antiserum (lanes 1, 2 and 5) were similarly analyzed. The volume of antiserum (diluted 1:10 with PBS) added was 1.0 µl. C indicates control; Free, free probe.

 
3.3 No significant activation of HSF by catecholamine or hypertensive agents
To determine whether hypertensive agents cause the activation of HSF1, we examined the HSE-binding activities of HSF1 in hearts perfused with the buffer containing epinephrine (Epin, 1.0 µmol/l), norepinephrine (Nor, 1.0 µmol/l), angiotensin II (Ang II, 10 nmol/l) or vasopressin (Vaso, 1.0 nmol/l) for 10 or 60 min. Concentrations of these agents in blood are increased in heart failure or hypotension. However, none of these agents activated the HSE-binding activities of HSF (Fig. 4). Significant high LVDP or significant high LV dP/dt caused by perfusion of Norepinephrine did not induce the activation of HSF.


Figure 4
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  		Fig. 4 Effects of catecholamine or hypertensive agents on DNA binding activity of HSF. Whole cell extracts from hearts perfused with the buffer containing epinephrine (Epin, 1.0 µmol/l), norepinephrine (Nor, 1.0 µmol/l), angiotensin II (Ang II, 10 nmol/l) or vasopressin (Vaso, 1.0 nmol/l) for 10 or 60 min, were analyzed by gel mobility shift assay using a radiolabeled HSE oligonucleotide. Results for control (C), heat-shocked (HS), or LV-overloaded hearts (LVEDP 30) are also shown.

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
The induction of HSP 70 by hemodynamic overload was first reported by Izumo et al. in the rat heart [9]. They showed that HSP 70 mRNA was induced within 30 min after ascending aortic coarctation. Delcayre et al. also demonstrated early and transient expression of HSP 70, HSP68, and HSP 58 mRNA in the rat heart after pressure or volume overload [5]. Induced expression by cardiac overload was also reported in the right ventricle of the rat, or in the left ventricle of newborn sheep [10,11]. However, they all used in vivo models and factors other than mechanical stress, such as catecholamine or hypertensive agents, which are released from organs other than the heart, can cause the induction of heat shock proteins.

In the present study, we demonstrated that the HSE-binding activity of HSF1 was directly induced by LV overload in isolated and perfused rat hearts. Moreover, we showed that the HSE-binding activity was not induced by perfusion with the buffer containing epinephrine, norepinephrine, angiotensin II, or vasopressin, the concentration of which in blood increases in heart failure or hypotension [2,28]. Significant high LVDP in hearts perfused with the buffer containing Norepinephrine, that is, increased afterload, did not activate HSF under the condition that LVEDP was kept in normal range. In contrast, increased LVEDP caused by increased volume of LV balloon, increased preload, induced the activation of HSF1. These findings suggest that increased preload as mechanical stress directly induces the heat shock gene expression in the heart.

Recently, Chang et al. have reported that the stretch in the heart results in activation of HSF1 and an increase in HSP72 mRNA through stretch-activated ion channels [29]. They reported that HSF1 activation was induced in Langendorff-perfused rat hearts with LVEDP of 5 to 10 mmHg that is within the normal range. In contrast, in working rat hearts, which are closer to a physiological perfusion, little activation of HSF were induced. They explained this discrepancy that mechanical stretch, which included stretch from insertion of the apical drain and placement of the ventricular balloon, initiated heat shock response in Langendorff perfusion [29,30]. However, as we have demonstrated with our Langendorff-perfused model, HSF activation was not induced in hearts perfused with LVEDP at 5 to 9 mmHg for 30 to 210 min in spite of inserting the apical drain and the ventricular balloon [7,26]. This observation was again confirmed in the present study. On the contrary, we could demonstrate that increased preload directly induces HSF activation, and that this induction was initiated as early as 10 min after perfusion with LVEDP at 30 mmHg.

Moalic et al. demonstrated the induction of HSP 70 mRNA in the heart of rats that were injected with phenylephrine or vasopressin 1 or 2 h earlier [31]. In their models, LVEDP, which was not shown, must be considerably high since the systolic blood pressure was shown to be more than 200 mmHg. It seems reasonable to suppose that mechanical stress due to high blood pressure caused by these hypertensive agents induced heat shock gene expression.

The detailed mechanisms inducing HSF1 activation by increased preload remain to be elucidated. An in vitro study showed a lack of stretch-induced expression of HSP 70 mRNA in cultured cardiac myocytes [18], suggesting other factors or subsequent events may be needed for the induction of heat shock genes. Moreover, we showed that the activation of HSF1 was not induced in a heart perfused with the buffer containing norepinephrine, the LVDP of which was significantly high, while the LVEDP of which was kept low. It is likely that subendocardial ischemia, which results from high LVEDP [32], contributes to the activation of HSF1 induced by LV overload.

In this paper, we showed that HSF1 was directly activated by increased preload as mechanical stress in the LV-overloaded heart. Further investigation of the mechanisms of HSP induction in the heart should provide a better understanding of mechanisms of cardiac hypertrophy, which results from overload, and may lead to progress in special treatment and prevention of cardiac hypertrophy, remodeling, and failure.

In summary, our data indicate that the HSE-binding activity of HSF1 was induced by increased preload of LV, but not induced by increased afterload of LV with perfusion of norepinephrine, in isolated and perfused rat hearts. Perfusion of the buffer containing epinephrine, angiotensin II, or vasopressin also failed to activate the HSF. These findings suggest that increased preload directly induces heat shock gene expression in the LV-overloaded heart.

Time for primary review 21 days.


   Acknowledgements
 
This study was supported in part by a grant from Core Research for Evolutional Science and Technology (CREST), the Japanese Science and Technology Cooperation (JST) and by Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science and Culture of Japan.


   Notes
 
1 Current address: Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Ube, Japan. Back

2 Current address: Department of Cardiovascular Surgery, Kokura Memorial Hospital, Kitakyushu, Japan. Back


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. Ruwhof C., van der Laarse A. Mechanical stress-induced cardiac hypertrophy: mechanisms and signal transduction pathways. Cardiovasc Res (2000) 47:23–37.[Abstract/Free Full Text]
  2. Cohn J.N. Cardiovascular medicine. Willerson J.T., ed. (1996) Tokyo: Churchill Livingstone. 947–979.
  3. Currie R.W., White F.P. Trauma-induced protein in rat tissues: a physiological role for a ‘heat shock’ protein? Science (1981) 214:72–73.[Abstract/Free Full Text]
  4. Dillmann W.H., Mehta H.B., Barrieux A., et al. Ischemia of the dog heart induces the appearance of a cardiac mRNA coding for a protein with migration characteristics similar to heat-shock/stress protein 71. Circ Res (1986) 59:110–114.[Abstract/Free Full Text]
  5. Delcayre C., Samuel J.L., Marotte F., et al. Synthesis of stress proteins in rat cardiac myocytes 2–4 days after imposition of hemodynamic overload. J Clin Invest (1988) 82:460–468.[ISI][Medline]
  6. Knowlton A.A., Brecher P., Apstein C.S. Rapid expression of heat shock protein in the rabbit after brief cardiac ischemia. J Clin Invest (1991) 87:139–147.[ISI][Medline]
  7. Nishizawa J., Nakai A., Higashi T., et al. Reperfusion causes significant activation of heat shock transcription factor 1 in ischemic rat heart. Circulation (1996) 94:2185–2192.[Abstract/Free Full Text]
  8. Latchman D.S. Handbook of experimental pharmacology. (1999).
  9. Izumo S., Nadal-Ginard B., Mahdavi V. Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proc Natl Acad Sci USA (1988) 85:339–343.[Abstract/Free Full Text]
  10. Katayose D., Isoyama S., Fujita H., Shibahara S. Separate regulation of heme oxygenase and heat shock protein 70 mRNA expression in the rat heart by hemodynamic stress. Biochem Biophys Res Commun (1993) 191:587–594.[CrossRef][ISI][Medline]
  11. Strandness E., Bernstein D. Developmental and afterload stress regulation of heat shock proteins in the ovine myocardium. Pediatr Res (1997) 41:51–56.[ISI][Medline]
  12. Currie R.W., Karmazyn M., Kloc M., Mailer K. Heat-shock response is associated with enhanced postischemic ventricular recovery. Circ Res (1988) 63:543–549.[Abstract/Free Full Text]
  13. Marber M.S., Mestril R., Chi S.H., et al. Overexpression of the rat inducible 70-kD heat stress protein in a transgenic mouse increases the resistance of the heart to ischemic injury. J Clin Invest (1995) 95:1446–1456.[ISI][Medline]
  14. Plumier J.C., Ross B.M., Currie R.W., et al. Transgenic mice expressing the human heat shock protein 70 have improved post-ischemic myocardial recovery. J Clin Invest (1995) 95:1854–1860.[ISI][Medline]
  15. Lau S., Patnaik N., Sayen M.R., Mestril R. Simultaneous overexpression of two stress proteins in rat cardiomyocytes and myogenic cells confers protection against ischemia-induced injury. Circulation (1997) 96:2287–2294.[Abstract/Free Full Text]
  16. Martin J.L., Mestril R., Hilal-Dandan R., Brunton L.L., Dillmann W.H. Small heat shock proteins and protection against ischemic injury in cardiac myocytes [see comments]. Circulation (1997) 96:4343–4348.[Abstract/Free Full Text]
  17. Heads R.J., Yellon D.M., Latchman D.S. Differential cytoprotection against heat stress or hypoxia following expression of specific stress protein genes in myogenic cells. J Mol Cell Cardiol (1995) 27:1669–1678.[CrossRef][ISI][Medline]
  18. Sadoshima J., Jahn L., Takahashi T., Kulik T.J., Izumo S. Molecular characterization of the stretch-induced adaptation of cultured cardiac cells. An in vitro model of load-induced cardiac hypertrophy. J Biol Chem (1992) 267:10551–10560.[Abstract/Free Full Text]
  19. Rabindran S.K., Giorgi G., Clos J., Wu C. Molecular cloning and expression of a human heat shock factor, HSF1. Proc Natl Acad Sci USA (1991) 88:6906–6910.[Abstract/Free Full Text]
  20. Sarge K.D., Zimarino V., Holm K., Wu C., Morimoto R.I. Cloning and characterization of two mouse heat shock factors with distinct inducible and constitutive DNA-binding ability. Genes Dev (1991) 5:1902–1911.[Abstract/Free Full Text]
  21. Schuetz T.J., Gallo G.J., Sheldon L., Tempst P., Kingston R.E. Isolation of a cDNA for HSF2: evidence for two heat shock factor genes in humans. Proc Natl Acad Sci USA (1991) 88:6911–6915.[Abstract/Free Full Text]
  22. Nakai A., Morimoto R.I. Characterization of a novel chicken heat shock transcription factor, heat shock factor 3, suggests a new regulatory pathway. Mol Cell Biol (1993) 13:1983–1997.[Abstract/Free Full Text]
  23. Nakai A., Tanabe M., Kawazoe Y., et al. HSF4, a new member of the human heat shock factor family which lacks properties of a transcriptional activator. Mol Cell Biol (1997) 17:469–481.[Abstract]
  24. Baler R., Dahl G., Voellmy R. Activation of human heat shock genes is accompanied by oligomerization, modification, and rapid translocation of heat shock transcription factor HSF1. Mol Cell Biol (1993) 13:2486–2496.[Abstract/Free Full Text]
  25. Sarge K.D., Murphy S.P., Morimoto R.I. Activation of heat shock gene transcription by heat shock factor 1 involves oligomerization, acquisition of DNA-binding activity, and nuclear localization and can occur in the absence of stress [published errata appear in Mol Cell Biol 1993 May;13(5):3122–3 and 1993 Jun;13(6):3838–9]. Mol Cell Biol (1993) 13:1392–1407.[Abstract/Free Full Text]
  26. Nishizawa J., Nakai A., Matsuda K., et al. Reactive oxygen species play an important role in the activation of heat shock factor 1 in ischemic-reperfused heart. Circulation (1999) 99:934–941.[Abstract/Free Full Text]
  27. Kinnunen P., Vuolteenaho O., Uusimaa P., Ruskoaho H. Passive mechanical stretch releases atrial natriuretic peptide from rat ventricular myocardium. Circ Res (1992) 70:1244–1253.[Abstract/Free Full Text]
  28. Swedberg K., Eneroth P., Kjekshus J., Wilhelmsen L. Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. Circulation (1990) 82:1730–1736.[Abstract/Free Full Text]
  29. Chang J., Wasser J.S., Cornelussen R.N., Knowlton A.A. Activation of heat-shock factor by stretch-activated channels in rat hearts. Circulation (2001) 104:209–214.[Abstract/Free Full Text]
  30. Knowlton A.A., Eberli F.R., Brecher P., et al. A single myocardial stretch or decreased systolic fiber shortening stimulates the expression of heat shock protein 70 in the isolated, erythrocyte-perfused rabbit heart. J Clin Invest (1991) 88:2018–2025.[ISI][Medline]
  31. Moalic J.M., Bauters C., Himbert D., et al. Phenylephrine, vasopressin and angiotensin II as determinants of proto-oncogene and heat-shock protein gene expression in adult rat heart and aorta. J Hypertens (1989) 7:195–201.[ISI][Medline]
  32. Chilian W.M., Marcus M.L. Coronary vascular adaptations to myocardial hypertrophy. Annu Rev Physiol (1987) 49:477–487.[CrossRef][ISI][Medline]

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