Circulation, Vol 88, 2849-2861, Copyright © 1993 by American Heart Association
FJ Villarreal, NN Kim, GD Ungab, MP Printz and WH Dillmann
BACKGROUND. Cardiac hypertrophy results in an increased deposition of the
extracellular matrix (ECM) proteins fibronectin and collagen. Recent
evidence indicates that angiotensin II (Ang II) might have an important
role in the development of myocardial fibrosis accompanying cardiac
hypertrophy. We sought to determine whether fibroblasts of cardiac origin
(isolated from neonatal and adult animals) express receptors for Ang II and
to examine the ability of this peptide to regulate fibronectin and collagen
gene expression in a cultured adult cardiac fibroblast cell preparation.
METHODS AND RESULTS. Binding of 125I-Ang II to both neonatal and adult
cardiac fibroblasts in culture was specific, reversible, and saturable,
with the receptor evenly distributed over the cell population. Competition
binding experiments with receptor-specific antagonists indicate that Ang II
receptors found on both fibroblast types were of the AT1 subtype. Analysis
of mRNA levels for the AT1 receptor indicates that adult cardiac
fibroblasts express higher levels of the message than neonatal fibroblasts
or cardiac myocytes. Addition of 10(-9) mol/L Ang II to adult cardiac
fibroblasts resulted in an induction of ECM proteins above control levels,
as determined through Northern blots and total collagen assays.
CONCLUSIONS. Results from this study indicate that neonatal and adult rat
cardiac fibroblasts in culture express AT1 receptors for Ang II. Ang II
stimulation of AT1 receptors results in an increased gene expression for
ECM proteins. These data suggest that Ang II might have important
regulatory roles over cardiac fibroblast function under normal and
pathological conditions.
ARTICLES
Identification of functional angiotensin II receptors on rat cardiac fibroblasts
Department of Medicine, University of California San Diego.
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K. T. Weber Extracellular Matrix Remodeling in Heart Failure : A Role for De Novo Angiotensin II Generation Circulation, December 2, 1997; 96(11): 4065 - 4082. [Full Text]
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W. W. Brooks, O. H. L. Bing, C. H. Conrad, L. O'Neill, M. T. Crow, E. G. Lakatta, D. E. Dostal, K. M. Baker, and M. O. Boluyt Captopril Modifies Gene Expression in Hypertrophied and Failing Hearts of Aged Spontaneously Hypertensive Rats Hypertension, December 1, 1997; 30(6): 1362 - 1368. [Abstract] [Full Text]
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T. Takizawa, M. Gu, A. V. Chobanian, and P. Brecher Effect of Nitric Oxide on DNA Replication Induced by Angiotensin II in Rat Cardiac Fibroblasts Hypertension, November 1, 1997; 30(5): 1035 - 1040. [Abstract] [Full Text]
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H. Yu, A. M. Gallagher, P. M. Garfin, and M. P. Printz Prostacyclin Release by Rat Cardiac Fibroblasts : Inhibition of Collagen Expression Hypertension, November 1, 1997; 30(5): 1047 - 1053. [Abstract] [Full Text]
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J. Fareh, R. M. Touyz, E. L. Schiffrin, and G. Thibault Cardiac Type-1 Angiotensin II Receptor Status in Deoxycorticosterone Acetate–Salt Hypertension in Rats Hypertension, November 1, 1997; 30(5): 1253 - 1259. [Abstract] [Full Text]
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C. M. Yang, V. Kandaswamy, D. Young, and S. Sen Changes in collagen phenotypes during progression and regression of cardiac hypertrophy Cardiovasc Res, November 1, 1997; 36(2): 236 - 245. [Abstract] [Full Text] [PDF]
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R. M. Touyz, J. Fareh, G. Thibault, and E. L. Schiffrin Intracellular Ca2+ Modulation by Angiotensin II and Endothelin-1 in Cardiomyocytes and Fibroblasts From Hypertrophied Hearts of Spontaneously Hypertensive Rats Hypertension, November 1, 1996; 28(5): 797 - 805. [Abstract] [Full Text]
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K. Kijima, H. Matsubara, S. Murasawa, K. Maruyama, Y. Mori, N. Ohkubo, I. Komuro, Y. Yazaki, T. Iwasaka, and M. Inada Mechanical Stretch Induces Enhanced Expression of Angiotensin II Receptor Subtypes in Neonatal Rat Cardiac Myocytes Circ. Res., October 1, 1996; 79(4): 887 - 897. [Abstract] [Full Text]
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C. G. Brilla, L. Matsubara, and K. T. Weber Advanced Hypertensive Heart Disease in Spontaneously Hypertensive Rats: Lisinopril-Mediated Regression of Myocardial Fibrosis Hypertension, August 1, 1996; 28(2): 269 - 275. [Abstract] [Full Text]
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S. Shanmugam, P. Corvol, and J.-M. Gasc Angiotensin II Type 2 Receptor mRNA Expression in the Developing Cardiopulmonary System of the Rat Hypertension, July 1, 1996; 28(1): 91 - 97. [Abstract] [Full Text]
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N. Iwai, T. Inagami, N. Ohmichi, and M. Kinoshita Renin Is Expressed in Rat Macrophage/Monocyte Cells Hypertension, March 1, 1996; 27(3): 399 - 403. [Abstract] [Full Text]
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J. Fareh, R. M. Touyz, E. L. Schiffrin, and G. Thibault Endothelin-1 and Angiotensin II Receptors in Cells From Rat Hypertrophied Heart : Receptor Regulation and Intracellular Ca2+ Modulation Circ. Res., February 1, 1996; 78(2): 302 - 311. [Abstract] [Full Text]
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Y. Furukawa, A. Matsumori, T. Hirozane, and S. Sasayama Angiotensin II Receptor Antagonist TCV-116 Reduces Graft Coronary Artery Disease and Preserves Graft Status in a Murine Model : A Comparative Study With Captopril Circulation, January 15, 1996; 93(2): 333 - 339. [Abstract] [Full Text]
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J. Fareh, R. M. Touyz, G. Thibault, and E. L. Schiffrin Basal and Angiotensin II–Induced Cytosolic Free Calcium in Adult Rat Cardiomyocytes and Fibroblasts After Volume Overload Hypertension, December 1, 1995; 26(6): 1149 - 1153. [Abstract] [Full Text]
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N. Iwai, H. Shimoike, and M. Kinoshita Cardiac Renin-Angiotensin System in the Hypertrophied Heart Circulation, November 1, 1995; 92(9): 2690 - 2696. [Abstract] [Full Text]
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A. Nicoletti, D. Heudes, N. Hinglais, M.-D. Appay, M. Philippe, C. Sassy-Prigent, J. Bariety, and J.-B. Michel Left Ventricular Fibrosis in Renovascular Hypertensive Rats : Effect of Losartan and Spironolactone Hypertension, July 1, 1995; 26(1): 101 - 111. [Abstract] [Full Text]
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J. Diez, C. Laviades, G. Mayor, M. J. Gil, and I. Monreal Increased Serum Concentrations of Procollagen Peptides in Essential Hypertension : Relation to Cardiac Alterations Circulation, March 1, 1995; 91(5): 1450 - 1456. [Abstract] [Full Text]
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V. Regitz-Zagrosek, N. Friedel, A. Heymann, P. Bauer, M. Neuß, A. Rolfs, C. Steffen, A. Hildebrandt, R. Hetzer, and E. Fleck Regulation, Chamber Localization, and Subtype Distribution of Angiotensin II Receptors in Human Hearts Circulation, March 1, 1995; 91(5): 1461 - 1471. [Abstract] [Full Text]
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F. J. Villarreal, D. A. MacKenna, J. H. Omens, and W. H. Dillmann Myocardial Remodeling in Hypertensive Ren-2 Transgenic Rats Hypertension, January 1, 1995; 25(1): 98 - 104. [Abstract] [Full Text]
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M. Sano, K. Fukuda, H. Kodama, J. Pan, M. Saito, J. Matsuzaki, T. Takahashi, S. Makino, T. Kato, and S. Ogawa Interleukin-6 Family of Cytokines Mediate Angiotensin II-induced Cardiac Hypertrophy in Rodent Cardiomyocytes J. Biol. Chem., September 15, 2000; 275(38): 29717 - 29723. [Abstract] [Full Text] [PDF]
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