Published online before print March 28, 2002, doi: 10.1161/01.RES.0000016963.43856.B1
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2002 American Heart Association, Inc.
Integrative Physiology |
Exercise Improves Postischemic Cardiac Function in Males but Not Females
Consequences of a Novel Sex-Specific Heat Shock Protein 70 Response
From The University of Western Ontario, School of Kinesiology (Z.P., E.G.N.), Faculty of Health Sciences, Lawson Health Research Institute (E.G.N.), and the Department of Pharmacology and Toxicology (J.V.H., M.K.), Faculty of Medicine and Dentistry, London, Ontario, Canada.
Correspondence to Dr Earl Noble, School of Kinesiology, Faculty of Health Sciences, The University of Western Ontario, London, Ontario, Canada N6A 3K7. E-mail enoble{at}uwo.ca
Exercise is a physiological inducer of the cardioprotective heat shock protein, Hsp70. The putative biological events involved in signaling this response exhibit sexual dimorphism. Thus, it was hypothesized that exercise-mediated induction of Hsp70 would demonstrate sex specificity. After treadmill running, male rats exhibited 2-fold greater levels of cardiac Hsp70 relative to the levels in gonadally intact female rats (P<0.001). Ovariectomized female rats exhibited exercise-mediated induction of Hsp70 similar to that observed for male rats, and estrogen treatment in these female rats reversed this effect (P<0.001). Attenuation of Hsp70 signaling by estrogen was non–receptor-mediated, possibly involving a cellular membrane–stabilizing mechanism of action. The physiological importance of this sex-specific hormone-mediated stress response is underscored by the disparity in functional adaptation in response to exercise between male rats and female rats. Exercise markedly improved postischemic left ventricular developed pressure, the maximal rate of contraction, and maximal rate of relaxation, and it reduced left ventricular end-diastolic pressure in male rats (P<0.001). No such benefit of exercise was observed in intact female rats. A causal role for Hsp70 in this sex-specific cardioprotective adaptation was indicated, inasmuch as ablation of Hsp70 induction with antisense oligonucleotides designed against Hsp70 transcripts attenuated improvement in the recovery of cardiac function in exercised male rats (P<0.05). Thus, the sex-specific hormone-mediated Hsp70 response to exercise results in cardioprotective adaptation, preferentially in male rats relative to female rats. These findings suggest that exercise may be more important for males than for females in defending against the effects of heart disease and offer a novel manner by which males may reduce the sex gap in susceptibility to adverse cardiac events.
Key Words: antisense oligonucleotides • heat shock proteins • hormones • sex • stress
This article has been cited by other articles:
 |
|
 |
|
  A. L. Orr, S. Huang, M. A. Roberts, J. C. Reed, S. Li, and X.-J. Li Sex-dependent Effect of BAG1 in Ameliorating Motor Deficits of Huntington Disease Transgenic Mice J. Biol. Chem., June 6, 2008; 283(23): 16027 - 16036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Brown, M. S. Johnson, C. J. Armstrong, J. M. Lynch, N. M. Caruso, L. B. Ehlers, M. Fleshner, R. L. Spencer, and R. L. Moore Short-term treadmill running in the rat: what kind of stressor is it? J Appl Physiol, December 1, 2007; 103(6): 1979 - 1985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. J. Melling, D. B. Thorp, K. J. Milne, M. P. Krause, and E. G. Noble Exercise-mediated regulation of Hsp70 expression following aerobic exercise training Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3692 - H3698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Quindry, K. L. Hamilton, J. P. French, Y. Lee, Z. Murlasits, N. Tumer, and S. K. Powers Exercise-induced HSP-72 elevation and cardioprotection against infarct and apoptosis J Appl Physiol, September 1, 2007; 103(3): 1056 - 1062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kohno, N. Takahashi, T. Shinohara, T. Ooie, K. Yufu, M. Nakagawa, H. Yonemochi, M. Hara, T. Saikawa, and H. Yoshimatsu Receptor-Mediated Suppression of Cardiac Heat-Shock Protein 72 Expression by Testosterone in Male Rat Heart Endocrinology, July 1, 2007; 148(7): 3148 - 3155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Thorp, J. V. Haist, J. Leppard, K. J. Milne, M. Karmazyn, and E. G. Noble Exercise training improves myocardial tolerance to ischemia in male but not in female rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R363 - R371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, S. Tsang, and T. M. Wong Testosterone Is Required for Delayed Cardioprotection and Enhanced Heat Shock Protein 70 Expression Induced by Preconditioning Endocrinology, October 1, 2006; 147(10): 4569 - 4577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Milne, D. B. Thorp, C. W. J. Melling, and E. G. Noble Castration inhibits exercise-induced accumulation of Hsp70 in male rodent hearts Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1610 - H1616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Johnson and M. Fleshner Releasing signals, secretory pathways, and immune function of endogenous extracellular heat shock protein 72 J. Leukoc. Biol., March 1, 2006; 79(3): 425 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. O. Reger, M. F. Barbe, M. Amin, B. F. Renna, L. A. Hewston, S. M. MacDonnell, S. R. Houser, and J. R. Libonati Myocardial hypoperfusion/reperfusion tolerance with exercise training in hypertension J Appl Physiol, February 1, 2006; 100(2): 541 - 547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bae and L. Zhang Gender Differences in Cardioprotection against Ischemia/Reperfusion Injury in Adult Rat Hearts: Focus on Akt and Protein Kinase C Signaling J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1125 - 1135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Starnes, A. M. Choilawala, R. P. Taylor, M. J. Nelson, and M. D. Delp Myocardial Heat Shock Protein 70 Expression in Young and Old Rats After Identical Exercise Programs J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2005; 60(8): 963 - 969. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Tosi, B. D. Boyan, and A. L. Boskey Does Sex Matter in Musculoskeletal Health? The Influence of Sex and Gender on Musculoskeletal Health J. Bone Joint Surg. Am., July 1, 2005; 87(7): 1631 - 1647. [Full Text] [PDF]
|
|
|
|
 |
|
 O. J. Kemi, P. M. Haram, J. P. Loennechen, J.-B. Osnes, T. Skomedal, U. Wisloff, and O. Ellingsen Moderate vs. high exercise intensity: Differential effects on aerobic fitness, cardiomyocyte contractility, and endothelial function Cardiovasc Res, July 1, 2005; 67(1): 161 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Moran, I. Blazquez, A. Saborido, and A. Megias Antioxidants and ecto-5'-nucleotidase are not involved in the training-induced cardioprotection against ischaemia-reperfusion injury Exp Physiol, July 1, 2005; 90(4): 507 - 517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A Brown, J. M Lynch, C. J Armstrong, N. M Caruso, L. B Ehlers, M. S Johnson, and R. L Moore Susceptibility of the heart to ischaemia-reperfusion injury and exercise-induced cardioprotection are sex-dependent in the rat J. Physiol., April 15, 2005; 564(2): 619 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mandal, E. Torsney, J. Poloniecki, A. J. Camm, Q. Xu, and M. Jahangiri Association of High Intracellular, But Not Serum, Heat Shock Protein 70 With Postoperative Atrial Fibrillation Ann. Thorac. Surg., March 1, 2005; 79(3): 865 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bupha-Intr and J. Wattanapermpool Cardioprotective effects of exercise training on myofilament calcium activation in ovariectomized rats J Appl Physiol, May 1, 2004; 96(5): 1755 - 1760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Lennon, J. Quindry, K. L. Hamilton, J. French, J. Staib, J. L. Mehta, and S. K. Powers Loss of exercise-induced cardioprotection after cessation of exercise J Appl Physiol, April 1, 2004; 96(4): 1299 - 1305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Chu, G. F. Egnaczyk, W. Zhao, S.-H. Jo, G.-C. Fan, J. E. Maggio, R.-P. Xiao, and E. G. Kranias Phosphoproteome Analysis of Cardiomyocytes Subjected to {beta}-Adrenergic Stimulation: Identification and Characterization of a Cardiac Heat Shock Protein p20 Circ. Res., February 6, 2004; 94(2): 184 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.-M. Backlin, C. Bredhult, and M. Olovsson Proliferative Effects of Estradiol, Progesterone, and Two CB Congeners and Their Metabolites on Gray Seal (Halichoerus grypus) Uterine Myocytes in Vitro Toxicol. Sci., September 1, 2003; 75(1): 154 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Voss, J. N. Stallone, M. Li, R. N. M. Cornelussen, P. Knuefermann, and A. A. Knowlton Gender differences in the expression of heat shock proteins: the effect of estrogen Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H687 - H692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Starnes, R. P. Taylor, and Y. Park Exercise improves postischemic function in aging hearts Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H347 - H351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-L. Huang, C.-P. Wu, Y.-L. Chen, B.-H. Kang, and Y.-C. Lin Heat stress attenuates air bubble-induced acute lung injury: a novel mechanism of diving acclimatization J Appl Physiol, April 1, 2003; 94(4): 1485 - 1490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Xi Exercise Does Not Protect the Female Heart: An Unconvincing Conclusion? Circ. Res., August 9, 2002; 91 (3): e2 - e2. [Full Text] [PDF]
|
|
|
|
|
|
K. J. Milne and E. G. Noble Exercise-induced elevation of HSP70 is intensity dependent J Appl Physiol, August 1, 2002; 93(2): 561 - 568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Paroo, M. J. Meredith, M. Locke, J. V. Haist, M. Karmazyn, and E. G. Noble Redox signaling of cardiac HSF1 DNA binding Am J Physiol Cell Physiol, August 1, 2002; 283(2): C404 - C411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. J. Benjamin and E. Christians Exercise, Estrogen, and Ischemic Cardioprotection by Heat Shock Protein 70 Circ. Res., May 3, 2002; 90(8): 833 - 835. [Full Text] [PDF]
|
|