Published online before print April 27, 2001, doi: 10.1161/hh0901.089882
© 2001 American Heart Association, Inc.
Clinical Research |
Cardiac Angiotensin II Formation in the Clinical Course of Heart Failure and Its Relationship With Left Ventricular Function
From Clinica Medica Generale e Cardiologia (G.G.N.S., M.B., I.C., S.V., M.C., M.L.P., B.B., I.B., G.P., P.A.M.), University of Florence, and Institute of Thoracic and Cardiovascular Surgery (T.T., M.M.), University of Siena, Italy.
Correspondence to Gian Gastone Neri Serneri, MD, Clinica Medica Generale e Cardiologia, University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
Abstract—In 76 patients with heart failure (HF) (New York Heart Association [NYHA] classes I through IV) and in 15 control subjects, cardiac angiotensin II (Ang II) generation and its relationship with left ventricular function were investigated by measuring aorta–coronary sinus concentration gradients of endogenous angiotensins and in a part of patients by studying 125I-labeled Ang I kinetics. Gene expression and cellular localization of the cardiac renin-angiotensin system components, the density of AT1 and AT2 on membranes and isolated myocytes, and the capacity of isolated myocytes for synthesizing the hypertrophying growth factors insulin-like growth factor-I (IGF-I) and endothelin (ET)-1 were also investigated on 22 HF explanted hearts (NYHA classes III and IV) and 7 nonfailing (NF) donor hearts. Ang II generation increased with progression of HF, and end-systolic wall stress was the only independent predictor of Ang II formation. Angiotensinogen and angiotensin-converting enzyme mRNA levels were elevated in HF hearts, whereas chymase levels were not, and mRNAs were almost exclusively expressed on nonmyocyte cells. Ang II was immunohistochemically detectable both on myocytes and interstitial cells. Binding studies showed that AT1 density on failing myocytes did not differ from that of NF myocytes, with preserved AT1/AT2 ratio. Conversely, AT1 density was lower in failing membranes than in NF ones. Ang II induced IGF-I and ET-1 synthesis by isolated NF myocytes, whereas failing myocytes were unable to respond to Ang II stimulation. This study demonstrates that (1) the clinical course of HF is associated with progressive increase in cardiac Ang II formation, (2) AT1 density does not change on failing myocytes, and (3) failing myocytes are unable to synthesize IGF-I and ET-1 in response to Ang II stimulation.>
Key Words: angiotensins • congestive heart failure • AT receptors • failing myocytes • cardiomyopathy
This article has been cited by other articles:
 |
|
 |
|
  N. Isidoro Tavares, P. Philip-Couderc, A. J. Baertschi, R. Lerch, and C. Montessuit Angiotensin II and tumour necrosis factor {alpha} as mediators of ATP-dependent potassium channel remodelling in post-infarction heart failure Cardiovasc Res, September 1, 2009; 83(4): 726 - 736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Krop, R. van Veghel, I. M. Garrelds, R. J.A. de Bruin, J. M.G. van Gool, A. H. van den Meiracker, M. Thio, P. L.A. van Daele, and A.H. J. Danser Cardiac Renin Levels Are Not Influenced by the Amount of Resident Mast Cells Hypertension, August 1, 2009; 54(2): 315 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Castro-Chaves, R. Fontes-Carvalho, M. Pintalhao, P. Pimentel-Nunes, and A. F. Leite-Moreira Angiotensin II-induced increase in myocardial distensibility and its modulation by the endocardial endothelium in the rabbit heart Exp Physiol, June 1, 2009; 94(6): 665 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Pellieux, C. Montessuit, I. Papageorgiou, and R. Lerch Angiotensin II downregulates the fatty acid oxidation pathway in adult rat cardiomyocytes via release of tumour necrosis factor-{alpha} Cardiovasc Res, May 1, 2009; 82(2): 341 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. de Denus, M. Zakrzewski-Jakubiak, M.-P. Dube, F. Belanger, S. Lepage, M.-H. Leblanc, D. Gossard, A. Ducharme, N. Racine, L. Whittom, et al. Effects of AGTR1 A1166C Gene Polymorphism in Patients with Heart Failure Treated with Candesartan Ann. Pharmacother., July 1, 2008; 42(7): 925 - 932. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. B. Ferreira, A. V. Bacurau, F. S. Evangelista, M. A. Coelho, E. M. Oliveira, D. E. Casarini, J. E. Krieger, and P. C. Brum The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2008; 294(1): R26 - R32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kilic, A. Bubikat, B. Gassner, H. A. Baba, and M. Kuhn Local Actions of Atrial Natriuretic Peptide Counteract Angiotensin II Stimulated Cardiac Remodeling Endocrinology, September 1, 2007; 148(9): 4162 - 4169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Xu, O. A. Carretero, C.-X. Lin, M. A. Cavasin, E. G. Shesely, J. J. Yang, T. L. Reudelhuber, and X.-P. Yang Role of cardiac overexpression of ANG II in the regulation of cardiac function and remodeling postmyocardial infarction Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1900 - H1907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Keidar, M. Kaplan, and A. Gamliel-Lazarovich ACE2 of the heart: From angiotensin I to angiotensin (1-7) Cardiovasc Res, February 1, 2007; 73(3): 463 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Mazzadi, X. Andre-Fouet, N. Costes, P. Croisille, D. Revel, and M. F. Janier Mechanisms leading to reversible mechanical dysfunction in severe CAD: alternatives to myocardial stunning Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2570 - H2582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Chung and G. Y.H. Lip Platelets and heart failure Eur. Heart J., November 2, 2006; 27(22): 2623 - 2631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Palomeque, L. Sapia, R. J. Hajjar, A. Mattiazzi, and M. Vila Petroff Angiotensin II-induced negative inotropy in rat ventricular myocytes: role of reactive oxygen species and p38 MAPK Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H96 - H106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Domenighetti, Q. Wang, M. Egger, S. M. Richards, T. Pedrazzini, and L. M.D. Delbridge Angiotensin II-Mediated Phenotypic Cardiomyocyte Remodeling Leads to Age-Dependent Cardiac Dysfunction and Failure Hypertension, August 1, 2005; 46(2): 426 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Ferrario, J. Jessup, M. C. Chappell, D. B. Averill, K. B. Brosnihan, E. A. Tallant, D. I. Diz, and P. E. Gallagher Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Receptor Blockers on Cardiac Angiotensin-Converting Enzyme 2 Circulation, May 24, 2005; 111(20): 2605 - 2610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Modesti, I. Bertolozzi, T. Gamberi, M. Marchetta, C. Lumachi, M. Coppo, F. Moroni, T. Toscano, G. Lucchese, G. F. Gensini, et al. Hyperglycemia Activates JAK2 Signaling Pathway in Human Failing Myocytes via Angiotensin II-Mediated Oxidative Stress Diabetes, February 1, 2005; 54(2): 394 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F.C. Schut, G. S. Bleumink, B. H.Ch. Stricker, A. Hofman, J. C.M. Witteman, H. A.P. Pols, J. W. Deckers, J. Deinum, and C. M. van Duijn Angiotensin converting enzyme insertion/deletion polymorphism and the risk of heart failure in hypertensive subjects Eur. Heart J., December 1, 2004; 25(23): 2143 - 2148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. van der Harst, M. Volbeda, A. A. Voors, H. Buikema, S. Wassmann, M. Bohm, G. Nickenig, and W. H. van Gilst Vascular Response to Angiotensin II Predicts Long-Term Prognosis in Patients Undergoing Coronary Artery Bypass Grafting Hypertension, December 1, 2004; 44(6): 930 - 934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 Y. Guo, E. Mascareno, and M. A. Q. Siddiqui Distinct Components of Janus Kinase/Signal Transducer and Activator of Transcription Signaling Pathway Mediate the Regulation of Systemic and Tissue Localized Renin-Angiotensin System Mol. Endocrinol., April 1, 2004; 18(4): 1033 - 1041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P A Modesti, G Polidori, I Bertolozzi, S Vanni, and I Cecioni Impairment of cardiopulmonary receptor sensitivity in the early phase of heart failure Heart, January 1, 2004; 90(1): 30 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Modesti, S. Vanni, I. Bertolozzi, I. Cecioni, C. Lumachi, A. M. Perna, M. Boddi, and G. F. Gensini Different Growth Factor Activation in the Right and Left Ventricles in Experimental Volume Overload Hypertension, January 1, 2004; 43(1): 101 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Averill, Y. Ishiyama, M. C. Chappell, and C. M. Ferrario Cardiac Angiotensin-(1-7) in Ischemic Cardiomyopathy Circulation, October 28, 2003; 108(17): 2141 - 2146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. McMullen, T. Shioi, L. Zhang, O. Tarnavski, M. C. Sherwood, P. M. Kang, and S. Izumo Phosphoinositide 3-kinase(p110{alpha}) plays a critical role for the induction of physiological, but not pathological, cardiac hypertrophy PNAS, October 14, 2003; 100(21): 12355 - 12360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Casal, J.-S. Silvestre, C. Delcayre, and A. M. Capponi Expression and Modulation of Steroidogenic Acute Regulatory Protein Messenger Ribonucleic Acid in Rat Cardiocytes and after Myocardial Infarction Endocrinology, May 1, 2003; 144(5): 1861 - 1868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shivakumar, D. E. Dostal, K. Boheler, K. M. Baker, and E. G. Lakatta Differential response of cardiac fibroblasts from young adult and senescent rats to ANG II Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1454 - H1459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
K.-D. Wagner, V. Essmann, K. Mydlak, M. Wirth, G. Gmehling, J. Bohlender, H. M. Stauss, J. Gunther, I. Schimke, and H. Scholz Decreased susceptibility of cardiac function to hypoxia-reoxygenation in renin-angiotensinogen transgenic rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R153 - R160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Saris, M. M.E.D. van den Eijnden, J. M.J. Lamers, P. R. Saxena, M. A.D.H. Schalekamp, and A.H. J. Danser Prorenin-Induced Myocyte Proliferation: No Role for Intracellular Angiotensin II Hypertension, February 1, 2002; 39(2): 573 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsubara Renin-Angiotensin System in Human Failing Hearts : Message From Nonmyocyte Cells to Myocytes Circ. Res., May 11, 2001; 88(9): 861 - 863. [Full Text] [PDF]
|
|
|
|
|
|
G. G. Neri Serneri, M. Boddi, P. A. Modesti, I. Cecioni, M. Coppo, L. Padeletti, A. Michelucci, A. Colella, and G. Galanti Increased Cardiac Sympathetic Activity and Insulin-Like Growth Factor-I Formation Are Associated With Physiological Hypertrophy in Athletes Circ. Res., November 23, 2001; 89(11): 977 - 982. [Abstract] [Full Text] [PDF]
|
|