help button home button Am J Pathol Epitomics
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Müller, D. N.
Right arrow Articles by Luft, F. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Müller, D. N.
Right arrow Articles by Luft, F. C.
(American Journal of Pathology. 2000;157:111-122.)
© 2000 American Society for Investigative Pathology

Regular Articles

Angiotensin II (AT1) Receptor Blockade Reduces Vascular Tissue Factor in Angiotensin II-Induced Cardiac Vasculopathy

Dominik N. Müller*, Eero M. A. Mervaala{dagger}, Ralf Dechend*, Anette Fiebeler§, Joon-Keun Park§, Folke Schmidt*, Jürgen Theuer*, Volker Breu, Nigel Mackman**, Thomas Luther||, Wolfgang Schneider{ddagger}, Dietrich Gulba*, Detlev Ganten{ddagger}, Hermann Haller§ and Friedrich C. Luft*

From the Franz Volhard Clinic,*
Medical Faculty of the Charité, Humboldt University of Berlin, Berlin, Germany; the Institute of Biomedicine,{dagger}
University of Helsinki, Helsinki, Finland; the Max Delbrück Center for Molecular Medicine,{ddagger}
Berlin, Germany; the Medical School Hannover,§
Hannover, Germany; F. Hoffmann-La Roche,
Basel, Switzerland; the Institute of Pathology,||
Technische Universität Dresden, Dresden, Germany; and the Department of Immunology,**
Scripps Research Institute, La Jolla, California

Tissue factor (TF), a main initiator of clotting, is up-regulated in vasculopathy. We tested the hypothesis that chronic in vivo angiotensin (ANG) II receptor AT1 receptor blockade inhibits TF expression in a model of ANG II-induced cardiac vasculopathy. Furthermore, we explored the mechanisms by examining transcription factor activation and analyzing the TF promoter. Untreated transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR) feature hypertension and severe left ventricular hypertrophy with focal areas of necrosis, and die at age 7 weeks. Plasma and cardiac ANG II was three- to fivefold increased compared to Sprague-Dawley rats. Chronic treatment with valsartan normalized blood pressure and coronary resistance completely, and ameliorated cardiac hypertrophy (P < 0.001). Valsartan prevented monocyte/macrophage infiltration, nuclear factor-{kappa}B (NF-{kappa}B) and activator protein-1 (AP-1) activation, and c-fos expression in dTGR hearts. NF-{kappa}B subunit p65 and TF expression was increased in the endothelium and media of cardiac vessels and markedly reduced by valsartan treatment. To analyze the mechanism of TF transcription, we then transfected human coronary artery smooth muscle cells and Chinese hamster ovary cells overexpressing the AT1 receptor with plasmids containing the human TF promoter and the luciferase reporter gene. ANG II induced the full-length TF promoter in both transfected cell lines. TF transcription was abolished by AT1 receptor blockade. Deletion of both AP-1 and NF-{kappa}B sites reduced ANG II-induced TF gene transcription completely, whereas the deletion of AP-1 sites reduced transcription. Thus, the present study clearly shows an aberrant TF expression in the endothelium and media in rats with ANG II-induced vasculopathy. The beneficial effects of AT1 receptor blockade in this model are mediated via the inhibition of NF-{kappa}B and AP-1 activation, thereby preventing TF expression, cardiac vasculopathy, and microinfarctions.




This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
N. Mackman, R. E. Tilley, and N. S. Key
Role of the Extrinsic Pathway of Blood Coagulation in Hemostasis and Thrombosis
Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1687 - 1693.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
V. C. Tu, H. Sun, G. T. Bowden, and Q. M. Chen
Involvement of oxidants and AP-1 in angiotensin II-activated NFAT3 transcription factor
Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1248 - C1255.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
A. Vidal, Y. Sun, S. K. Bhattacharya, R. A. Ahokas, I. C. Gerling, and K. T. Weber
Calcium paradox of aldosteronism and the role of the parathyroid glands
Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H286 - H294.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
A. W.J.H. Dielis, M. Smid, H. M.H. Spronk, K. Hamulyak, A. A. Kroon, H. ten Cate, and P. W. de Leeuw
The Prothrombotic Paradox of Hypertension: Role of the Renin-Angiotensin and Kallikrein-Kinin Systems
Hypertension, December 1, 2005; 46(6): 1236 - 1242.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. Wang, R. Han, I. Lee, A. S. Hancock, G. Xiong, M. D. Gunn, and W. W. Hancock
Permanent Survival of Fully MHC-Mismatched Islet Allografts by Targeting a Single Chemokine Receptor Pathway
J. Immunol., November 15, 2005; 175(10): 6311 - 6318.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. Wang, J. Zhang, G. Spinetti, L.-Q. Jiang, R. Monticone, D. Zhao, L. Cheng, M. Krawczyk, M. Talan, G. Pintus, et al.
Angiotensin II Activates Matrix Metalloproteinase Type II and Mimics Age-Associated Carotid Arterial Remodeling in Young Rats
Am. J. Pathol., November 1, 2005; 167(5): 1429 - 1442.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
B. Pilz, E. Shagdarsuren, M. Wellner, A. Fiebeler, R. Dechend, P. Gratze, S. Meiners, D. L. Feldman, R. L. Webb, I. M. Garrelds, et al.
Aliskiren, a Human Renin Inhibitor, Ameliorates Cardiac and Renal Damage in Double-Transgenic Rats
Hypertension, September 1, 2005; 46(3): 569 - 576.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
G. G. Neri Serneri, M. Boddi, P. A. Modesti, M. Coppo, I. Cecioni, T. Toscano, M. L. Papa, M. Bandinelli, G. F. Lisi, and M. Chiavarelli
Cardiac Angiotensin II Participates in Coronary Microvessel Inflammation of Unstable Angina and Strengthens the Immunomediated Component
Circ. Res., June 25, 2004; 94(12): 1630 - 1637.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
K. T. Weber
From Inflammation to Fibrosis: A Stiff Stretch of Highway
Hypertension, April 1, 2004; 43(4): 716 - 719.
[Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
D. N. Muller, J. Theuer, E. Shagdarsuren, E. Kaergel, H. Honeck, J.-K. Park, M. Markovic, E. Barbosa-Sicard, R. Dechend, M. Wellner, et al.
A Peroxisome Proliferator-Activated Receptor-{alpha} Activator Induces Renal CYP2C23 Activity and Protects from Angiotensin II-Induced Renal Injury
Am. J. Pathol., February 1, 2004; 164(2): 521 - 532.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
P. Finckenberg, K. Inkinen, J. Ahonen, S. Merasto, M. Louhelainen, H. Vapaatalo, D. Muller, D. Ganten, F. Luft, and E. Mervaala
Angiotensin II Induces Connective Tissue Growth Factor Gene Expression via Calcineurin-Dependent Pathways
Am. J. Pathol., July 1, 2003; 163(1): 355 - 366.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
D. N. Muller, A. Mullally, R. Dechend, J.-K. Park, A. Fiebeler, B. Pilz, B.-M. Loffler, D. Blum-Kaelin, S. Masur, H. Dehmlow, et al.
Endothelin-Converting Enzyme Inhibition Ameliorates Angiotensin II-Induced Cardiac Damage
Hypertension, December 1, 2002; 40(6): 840 - 846.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
D. N. Muller, E. Shagdarsuren, J.-K. Park, R. Dechend, E. Mervaala, F. Hampich, A. Fiebeler, X. Ju, P. Finckenberg, J. Theuer, et al.
Immunosuppressive Treatment Protects Against Angiotensin II-Induced Renal Damage
Am. J. Pathol., November 1, 2002; 161(5): 1679 - 1693.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
L. Kalinowski, T. Matys, E. Chabielska, W. Buczko, and T. Malinski
Angiotensin II AT1 Receptor Antagonists Inhibit Platelet Adhesion and Aggregation by Nitric Oxide Release
Hypertension, October 1, 2002; 40(4): 521 - 527.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. D. Schecter, A. B. Berman, L. Yi, A. Mosoian, C. M. McManus, J. W. Berman, M. E. Klotman, and M. B. Taubman
HIV envelope gp120 activates human arterial smooth muscle cells
PNAS, August 10, 2001; (2001) 181328798.
[Abstract] [Full Text] [PDF]

Home page
 Journal of Renin-Angiotensin-Aldosterone SystemHome page
M.-S. Zhou, A. Adam, and L. Raij
Review: Interaction among angiotensin II, nitric oxide and oxidative stress
Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1_suppl): S59 - S63.
[PDF]

Home page
 HypertensionHome page
Z. J. Cheng, T. Vaskonen, I. Tikkanen, K. Nurminen, H. Ruskoaho, H. Vapaatalo, D. Muller, J.-K. Park, F. C. Luft, and E. M. A. Mervaala
Endothelial Dysfunction and Salt-Sensitive Hypertension in Spontaneously Diabetic Goto-Kakizaki Rats
Hypertension, February 1, 2001; 37(2): 433 - 439.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
F. C. Luft
Workshop: Mechanisms and Cardiovascular Damage in Hypertension
Hypertension, February 1, 2001; 37(2): 594 - 598.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
A. Fiebeler, F. Schmidt, D. N. Muller, J.-K. Park, R. Dechend, M. Bieringer, E. Shagdarsuren, V. Breu, H. Haller, and F. C. Luft
Mineralocorticoid Receptor Affects AP-1 and Nuclear Factor-{{kappa}}B Activation in Angiotensin II-Induced Cardiac Injury
Hypertension, February 1, 2001; 37(2): 787 - 793.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
T. S. Edgington
Association between the Molecular Pathobiology of Essential Hypertension and Thrombotic Diseases
Am. J. Pathol., July 1, 2000; 157(1): 5 - 6.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. D. Schecter, A. B. Berman, L. Yi, A. Mosoian, C. M. McManus, J. W. Berman, M. E. Klotman, and M. B. Taubman
HIV envelope gp120 activates human arterial smooth muscle cells
PNAS, August 28, 2001; 98(18): 10142 - 10147.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2000 by the American Society for Investigative Pathology.