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Physiol. Rev. 79: 215-262, 1999;
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PHYSIOLOGICAL REVIEWS   Vol. 79 No. 1 January 1999, pp. 215-262
Copyright ©1999 The American Physiological Society

Molecular Mechanisms of Myocardial Remodeling

BERNARD SWYNGHEDAUW

Institut National de la Santé et de la Recherche Médicale U. 127, Hôpital Lariboisière, Paris, France

Swynghedauw, Bernard. Molecular Mechanisms of Myocardial Remodeling. Physiol. Rev. 79: 215-262, 1999. --- "Remodeling" implies changes that result in rearrangement of normally existing structures. This review focuses only on permanent modifications in relation to clinical dysfunction in cardiac remodeling (CR) secondary to myocardial infarction (MI) and/or arterial hypertension and includes a special section on the senescent heart, since CR is mainly a disease of the elderly. From a biological point of view, CR is determined by 1 ) the general process of adaptation which allows both the myocyte and the collagen network to adapt to new working conditions; 2) ventricular fibrosis, i.e., increased collagen concentration, which is multifactorial and caused by senescence, ischemia, various hormones, and/or inflammatory processes; 3) cell death, a parameter linked to fibrosis, which is usually due to necrosis and apoptosis and occurs in nearly all models of CR. The process of adaptation is associated with various changes in genetic expression, including a general activation that causes hypertrophy, isogenic shifts which result in the appearance of a slow isomyosin, and a new Na+-K+-ATPase with a low affinity for sodium, reactivation of genes encoding for atrial natriuretic fator and the renin-angiotensin system, and a diminished concentration of sarcoplasmic reticulum Ca2+-ATPase, beta -adrenergic receptors, and the potassium channel responsible for transient outward current. From a clinical point of view, fibrosis is for the moment a major marker for cardiac failure and a crucial determinant of myocardial heterogeneity, increasing diastolic stiffness, and the propensity for reentry arrhythmias. In addition, systolic dysfunction is facilitated by slowing of the calcium transient and the downregulation of the entire adrenergic system. Modifications of intracellular calcium movements are the main determinants of the triggered activity and automaticity that cause arrhythmias and alterations in relaxation.




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J. Exp. Biol., June 15, 2006; 209(12): 2320 - 2327.
[Abstract] [Full Text] [PDF]

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 Eur J Heart FailHome page
J. R. Wilding, C. A. Lygate, K. E. Davies, S. Neubauer, and K. Clarke
MLP accumulation and remodelling in the infarcted rat heart
Eur J Heart Fail, June 1, 2006; 8(4): 343 - 346.
[Abstract] [Full Text] [PDF]

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 FASEB J.Home page
Y. Xu, S. J. Williams, D. O'Brien, and S. T. Davidge
Hypoxia or nutrient restriction during pregnancy in rats leads to progressive cardiac remodeling and impairs postischemic recovery in adult male offspring
FASEB J, June 1, 2006; 20(8): 1251 - 1253.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
M. F. Berry, A. J. Engler, Y. J. Woo, T. J. Pirolli, L. T. Bish, V. Jayasankar, K. J. Morine, T. J. Gardner, D. E. Discher, and H. L. Sweeney
Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance
Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2196 - H2203.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
M. Fedele, V. Fidanza, S. Battista, F. Pentimalli, A. J.P. Klein-Szanto, R. Visone, I. De Martino, A. Curcio, C. Morisco, L. Del Vecchio, et al.
Haploinsufficiency of the hmga1 gene causes cardiac hypertrophy and myelo-lymphoproliferative disorders in mice.
Cancer Res., March 1, 2006; 66(5): 2536 - 2543.
[Abstract] [Full Text] [PDF]

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 Eur J Heart FailHome page
F. Alla, A. Kearney-Schwartz, A. Radauceanu, S. D. Dores, B. Dousset, and F. Zannad
Early changes in serum markers of cardiac extra-cellular matrix turnover in patients with uncomplicated hypertension and type II diabetes
Eur J Heart Fail, March 1, 2006; 8(2): 147 - 153.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
K. R. Hallows, A. C. Fitch, C. A. Richardson, P. R. Reynolds, J. P. Clancy, P. C. Dagher, L. A. Witters, J. K. Kolls, and J. M. Pilewski
Up-regulation of AMP-activated Kinase by Dysfunctional Cystic Fibrosis Transmembrane Conductance Regulator in Cystic Fibrosis Airway Epithelial Cells Mitigates Excessive Inflammation
J. Biol. Chem., February 17, 2006; 281(7): 4231 - 4241.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
T. Ago and J. Sadoshima
GDF15, a Cardioprotective TGF-{beta} Superfamily Protein
Circ. Res., February 17, 2006; 98(3): 294 - 297.
[Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
M. Matsumoto-Ida, Y. Takimoto, T. Aoyama, M. Akao, T. Takeda, and T. Kita
Activation of TGF-{beta}1-TAK1-p38 MAPK pathway in spared cardiomyocytes is involved in left ventricular remodeling after myocardial infarction in rats
Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H709 - H715.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
H. Nakajima, H. O. Nakajima, K. Dembowsky, K. B.S. Pasumarthi, and L. J. Field
Cardiomyocyte Cell Cycle Activation Ameliorates Fibrosis in the Atrium
Circ. Res., January 6, 2006; 98(1): 141 - 148.
[Abstract] [Full Text] [PDF]

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 Eur Heart JHome page
C. D'Ascia, A. Cittadini, M. G. Monti, G. Riccio, and L. Sacca
Effects of biventricular pacing on interstitial remodelling, tumor necrosis factor-{alpha} expression, and apoptotic death in failing human myocardium
Eur. Heart J., January 2, 2006; 27(2): 201 - 206.
[Abstract] [Full Text] [PDF]

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 Toxicol PatholHome page
Y. J. Kang
Cardiac Hypertrophy: A Risk Factor for QT-Prolongation and Cardiac Sudden Death
Toxicol Pathol, January 1, 2006; 34(1): 58 - 66.
[Abstract] [Full Text] [PDF]

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 Phil Trans R Soc BHome page
A. Cave, D. Grieve, S. Johar, M. Zhang, and A. M Shah
NADPH oxidase-derived reactive oxygen species in cardiac pathophysiology
Phil Trans R Soc B, December 29, 2005; 360(1464): 2327 - 2334.
[Abstract] [Full Text] [PDF]

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 Exp. Biol. Med.Home page
M. Pavlovic, A. Schaller, B. Steiner, P. Berdat, T. Carrel, J.-P. Pfammatter, R. A. Ammann, and S. Gallati
Gender Modulates the Expression of Calcium-Regulating Proteins in Pediatric Atrial Myocardium
Experimental Biology and Medicine, December 1, 2005; 230(11): 853 - 859.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
C. E. Mascio, A. K. Olison, J. C. Ralphe, R. J. Tomanek, T. D. Scholz, and J. L. Segar
Myocardial vascular and metabolic adaptations in chronically anemic fetal sheep
Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1736 - R1745.
[Abstract] [Full Text] [PDF]

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 Exp PhysiolHome page
S.-S. Zhou, J. Yang, Y.-Q. Li, L.-Y. Zhao, M. Xu, and Y.-F. Ding
Effect of Cl- channel blockers on aconitine-induced arrhythmias in rat heart
Exp Physiol, November 1, 2005; 90(6): 865 - 872.
[Abstract] [Full Text] [PDF]

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 ChestHome page
E. Fung, R. R. Fiscus, A. P. C. Yim, G. D. Angelini, and A. A. Arifi
The Potential Use of Type-5 Phosphodiesterase Inhibitors in Coronary Artery Bypass Graft Surgery
Chest, October 1, 2005; 128(4): 3065 - 3073.
[Abstract] [Full Text] [PDF]

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 Physiol. Rev.Home page
J. M. Nerbonne and R. S. Kass
Molecular Physiology of Cardiac Repolarization
Physiol Rev, October 1, 2005; 85(4): 1205 - 1253.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. Vornanen, M. Hassinen, H. Koskinen, and A. Krasnov
Steady-state effects of temperature acclimation on the transcriptome of the rainbow trout heart
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R1177 - R1184.
[Abstract] [Full Text] [PDF]

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 Journal of Renin-Angiotensin-Aldosterone SystemHome page
I. Haulica, W. Bild, and D. N Serban
Review: Angiotensin Peptides and their Pleiotropic Actions
Journal of Renin-Angiotensin-Aldosterone System, September 1, 2005; 6(3): 121 - 131.
[Abstract] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
R. Saeedi, M. Grist, R. B. Wambolt, A. Bescond-Jacquet, A. Lucien, and M. F. Allard
Trimetazidine Normalizes Postischemic Function of Hypertrophied Rat Hearts
J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 446 - 454.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
T. Nakamura, K. Matsumoto, S. Mizuno, Y. Sawa, H. Matsuda, and T. Nakamura
Hepatocyte growth factor prevents tissue fibrosis, remodeling, and dysfunction in cardiomyopathic hamster hearts
Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2131 - H2139.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
A. Deten, G. Marx, W. Briest, H. Christian Volz, and H.-G. Zimmer
Heart function and molecular biological parameters are comparable in young adult and aged rats after chronic myocardial infarction
Cardiovasc Res, May 1, 2005; 66(2): 364 - 373.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
M. Mendez and M. C. LaPointe
PGE2-induced hypertrophy of cardiac myocytes involves EP4 receptor-dependent activation of p42/44 MAPK and EGFR transactivation
Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2111 - H2117.
[Abstract] [Full Text] [PDF]

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 Eur J Heart FailHome page
U. Dahlstrom
Frequent non-cardiac comorbidities in patients with chronic heart failure
Eur J Heart Fail, March 16, 2005; 7(3): 309 - 316.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
P. Martinka, J. Fielitz, A. Patzak, V. Regitz-Zagrosek, P. B. Persson, and H. M. Stauss
Mechanisms of blood pressure variability-induced cardiac hypertrophy and dysfunction in mice with impaired baroreflex
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2005; 288(3): R767 - R776.
[Abstract] [Full Text] [PDF]


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