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(Circulation. 1997;96:4065-4082.)
© 1997 American Heart Association, Inc.
Articles |
Extracellular Matrix Remodeling in Heart Failure
A Role for De Novo Angiotensin II Generation
From the Division of Cardiology, Department of Internal Medicine, University of Missouri Health Sciences Center, Columbia.
Correspondence to Karl T. Weber, MD, Division of Cardiology, MA432 Medical Sciences Building, University of Missouri Health Sciences Center, Columbia, MO 65212.
Key Words: angiotensin • collagen • diastole • heart failure • remodeling
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Introduction |
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Heart failure is a major health problem worldwide. In the United States, it represents the number one hospital discharge diagnosis among elderly persons each year. It appears most commonly in patients with previous MI.1,2 The chronically failing heart of ischemic origin is characterized by iterations in tissue structure, particularly fibrous tissue formation, that appear in infarcted and noninfarcted myocardium of both right and left ventricles.3,4 In other words, fibrosis appears at the site of MI as well as remote from it. Fibrosis remote from the infarct site is considered "the major cause of ventricular remodeling" in ischemic cardiomyopathy.4 Such an adverse accumulation of extracellular matrix initially raises myocardial stiffness; its continued accumulation further increases stiffness and impairs contractile behavior.5–10 Elucidating cellular and molecular mechanisms responsible for accumulation of extracellular matrix is essential to designing cardioprotective and reparative strategies that could prevent or regress fibrosis, respectively, after infarction.11,12
ACE inhibition has proved effective in reducing mortal and morbid
events, improving symptomatic status, and attenuating the
progressive nature of cardiac failure in symptomatic
patients with ventricular diastolic and/or
systolic dysfunction in whom activation of the circulating RAAS
is present.1,13,14 ACE
inhibitor–mediated reductions in circulating Ang II and
aldosterone no doubt contribute to this salutary response.
This would include an attenuation of well-recognized endocrine
properties of these hormones, such as altered sodium homeostasis and
vascular tonicity, and their adverse influence on matrix structure of
atria and ventricles.15–20 Collectively, these
adverse responses to RAAS effector hormones contribute to the
progressive nature of chronic cardiac
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 R Ferrara, F Mastrorilli, G Pasanisi, S Censi, N D'aiello, A Fucili, M Valgimigli, and R Ferrari Neurohormonal modulation in chronic heart failure Eur. Heart J. Suppl., April 1, 2002; 4(suppl_D): D3 - D11. [Abstract] [PDF]
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D. Fraccarollo, J. Bauersachs, M. Kellner, P. Galuppo, and G. Ertl Cardioprotection by long-term ETA receptor blockade and ACE inhibition in rats with congestive heart failure: mono- versus combination therapy Cardiovasc Res, April 1, 2002; 54(1): 85 - 94. [Abstract] [Full Text] [PDF]
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R. T. Cowling, D. Gurantz, J. Peng, W. H. Dillmann, and B. H. Greenberg Transcription Factor NF-kappa B Is Necessary for Up-regulation of Type 1 Angiotensin II Receptor mRNA in Rat Cardiac Fibroblasts Treated with Tumor Necrosis Factor-alpha or Interleukin-1beta J. Biol. Chem., February 15, 2002; 277(8): 5719 - 5724. [Abstract] [Full Text] [PDF]
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 M. LIU, M. SUGA, A. A. MACLEAN, J. A. ST. GEORGE, D. W. SOUZA, and S. KESHAVJEE Soluble Transforming Growth Factor-beta Type III Receptor Gene Transfection Inhibits Fibrous Airway Obliteration in a Rat Model of Bronchiolitis Obliterans Am. J. Respir. Crit. Care Med., February 1, 2002; 165(3): 419 - 423. [Abstract] [Full Text] [PDF]
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J. K. Bendall, A. C. Cave, C. Heymes, N. Gall, and A. M. Shah Pivotal Role of a gp91phox-Containing NADPH Oxidase in Angiotensin II-Induced Cardiac Hypertrophy in Mice Circulation, January 22, 2002; 105(3): 293 - 296. [Abstract] [Full Text] [PDF]
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K. T. Weber Aldosterone in Congestive Heart Failure N. Engl. J. Med., December 6, 2001; 345(23): 1689 - 1697. [Full Text] [PDF]
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 F. W. Bowen, S. C. Jones, N. Narula, M. G. St. John Sutton, T. Plappert, L. H. Edmunds Jr, and I. M.C. Dixon Restraining acute infarct expansion decreases collagenase activity in borderzone myocardium Ann. Thorac. Surg., December 1, 2001; 72(6): 1950 - 1956. [Abstract] [Full Text] [PDF]
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E. D. Frohlich Local Hemodynamic Changes in Hypertension: Insights for Therapeutic Preservation of Target Organs Hypertension, December 1, 2001; 38(6): 1388 - 1394. [Abstract] [Full Text] [PDF]
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S. Capomolla, G. Pinna, O. Febo, A. Caporotondi, G. Guazzotti, M. T. La Rovere, M. Gnemmi, A. Mortara, R. Maestri, and F. Cobelli Echo-Doppler mitral flow monitoring: an operative tool to evaluate day-to-day tolerance to and effectiveness of beta-adrenergic blocking agent therapy in patients with chronic heart failure J. Am. Coll. Cardiol., November 15, 2001; 38(6): 1675 - 1684. [Abstract] [Full Text] [PDF]
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J. I. Nwogu, D. Geenen, M. Bean, M. C. Brenner, X. Huang, and P. M. Buttrick Inhibition of Collagen Synthesis With Prolyl 4-Hydroxylase Inhibitor Improves Left Ventricular Function and Alters the Pattern of Left Ventricular Dilatation After Myocardial Infarction Circulation, October 30, 2001; 104(18): 2216 - 2221. [Abstract] [Full Text] [PDF]
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J. Bauersachs, P. Galuppo, D. Fraccarollo, M. Christ, and G. Ertl Improvement of Left Ventricular Remodeling and Function by Hydroxymethylglutaryl Coenzyme A Reductase Inhibition With Cerivastatin in Rats With Heart Failure After Myocardial Infarction Circulation, August 28, 2001; 104(9): 982 - 985. [Abstract] [Full Text] [PDF]
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P. R Kalra, S. D Anker, and A. J.S Coats Water and sodium regulation in chronic heart failure: the role of natriuretic peptides and vasopressin Cardiovasc Res, August 15, 2001; 51(3): 495 - 509. [Full Text] [PDF]
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S. Ichihara, T. Senbonmatsu, E. Price Jr, T. Ichiki, F. A. Gaffney, and T. Inagami Angiotensin II Type 2 Receptor Is Essential for Left Ventricular Hypertrophy and Cardiac Fibrosis in Chronic Angiotensin II-Induced Hypertension Circulation, July 17, 2001; 104(3): 346 - 351. [Abstract] [Full Text] [PDF]
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G. de Simone, F. Pasanisi, and F. Contaldo Link of Nonhemodynamic Factors to Hemodynamic Determinants of Left Ventricular Hypertrophy Hypertension, July 1, 2001; 38(1): 13 - 18. [Abstract] [Full Text] [PDF]
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P. J Lijnen, V. V Petrov, and R. H Fagard Angiotensin II-induced stimulation of collagen secretion and production in cardiac fibroblasts is mediated via angiotensin II subtype 1 receptors Journal of Renin-Angiotensin-Aldosterone System, June 1, 2001; 2(2): 117 - 122. [Abstract] [PDF]
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R. Ferrari Pathophysiological vs biochemical ischaemia: a key to transition from reversible to irreversible damage Eur. Heart J. Suppl., June 1, 2001; 3(suppl_C): C2 - C10. [Abstract] [PDF]
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T. Omland, W. Johnson, M. B. Gordon, and M. A. Creager Endothelial function during stimulation of renin-angiotensin system by low-sodium diet in humans Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2248 - H2254. [Abstract] [Full Text] [PDF]
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H. Yoshida, K. Tanonaka, Y. Miyamoto, T. Abe, M. Takahashi, M. B Anand-Srivastava, and S. Takeo Characterization of cardiac myocyte and tissue {beta}-adrenergic signal transduction in rats with heart failure Cardiovasc Res, April 1, 2001; 50(1): 34 - 45. [Abstract] [Full Text] [PDF]
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 J. Varagic, D. Susic, and E. D. Frohlich Cardiovasc Pharmacol Therapeut 6(1):57-63, 2001 Low-Dose ACE with Alphaor Beta-Adrenergic Receptor Inhibitors Have Beneficial SHR Cardiovascular Effects Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2001; 6(1): 57 - 63. [Abstract] [PDF]
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E. D Frohlich Review: Promise of prevention and reversal of target organ involvement in hypertension Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1_suppl): S4 - S9. [PDF]
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G. J. Perry, T. Mori, C.-C. Wei, X. Y. Xu, Y.-F. Chen, S. Oparil, P. Lucchesi, and L. J. Dell'Italia Genetic Variation in Angiotensin-Converting Enzyme Does Not Prevent Development of Cardiac Hypertrophy or Upregulation of Angiotensin II in Response to Aortocaval Fistula Circulation, February 20, 2001; 103(7): 1012 - 1016. [Abstract] [Full Text] [PDF]
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K. T Weber and Yao Sun Recruitable ACE and tissue repair in the infarcted heart Journal of Renin-Angiotensin-Aldosterone System, December 1, 2000; 1(4): 295 - 303. [PDF]
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V. V Petrov, R. H Fagard, and P. J Lijnen Transforming growth factor-{beta}1 induces angiotensin-converting enzyme synthesis in rat cardiac fibroblasts during their differentiation to myofibroblasts Journal of Renin-Angiotensin-Aldosterone System, December 1, 2000; 1(4): 342 - 352. [Abstract] [PDF]
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G. Pons-Llado, M. Ballester, X. Borras, F. Carreras, I. Carrio, J. Lopez-Contreras, A. Roca-Cusachs, J. Marrugat, and J. Narula Myocardial cell damage in human hypertension J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2198 - 2203. [Abstract] [Full Text] [PDF]
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J. Hao, B. Wang, S. C. Jones, D. S. Jassal, and I. M. C. Dixon Interaction between angiotensin II and Smad proteins in fibroblasts in failing heart and in vitro Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H3020 - H3030. [Abstract] [Full Text] [PDF]
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