This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hambrecht, R. Articles by Schuler, G. Search for Related Content PubMed PubMed Citation Articles by Hambrecht, R. Articles by Schuler, G.

CLINICAL STUDY: HEART FAILURE

Reduction of insulin-like growth factor-I expression in the skeletal muscle of noncachectic patients with chronic heart failure

Rainer Hambrecht, MD^*,*, Paul Christian Schulze, MD^*, Stephan Gielen, MD^*, Axel Linke, MD^*, Sven Möbius-Winkler, MD^*, Jiangtao Yu, MD^*, J.ürgen Kratzsch, MD, Gerhard Baldauf, MD, Martin W. Busse, MD^||, Andreas Schubert, PhD, Volker Adams, PhD^* and Gerhard Schuler, MD^*

^* University of Leipzig–Heart Center, Department of Cardiology; Leipzig, Germany
Department of Cardiac Surgery, University of Leipzig–Heart Center, Leipzig, Germany
Department of Radiology, University of Leipzig–Heart Center, Leipzig, Germany
Institute of Clinical Chemistry, Leipzig, Germany
^|| Institute of Sport Medicine, Leipzig, Germany

Manuscript received September 17, 2001; revised manuscript received December 28, 2001, accepted January 11, 2002.

^* Reprint requests and correspondence: Dr. Rainer Hambrecht, Professor of Medicine, Heart Center, University of Leipzig, Strümpellstr. 39, 04289 Leipzig, Germany.
hamr{at}medizin.uni-leipzig.de

OBJECTIVES: We sought to assess the role of insulin-like growth factor-I (IGF-I) in muscle wasting in chronic heart failure (CHF), serum concentrations and local muscular IGF-I expression were determined in patients with severe CHF.

BACKGROUND: Chronic heart failure is associated with progressive muscle atrophy, leading to cardiac cachexia. Skeletal muscle disuse and inflammatory activation with elevated cytokine levels have been implicated; however, the pathomechanism involved remains largely unknown.

METHODS: Serum levels of IGF-I were measured by competitive solid phase immunoassay in 47 patients with severe CHF (left ventricular ejection fraction 30%) and 15 age-matched healthy subjects (HS). Insulin-like growth factor-I and IGF-I receptor expression were assessed in vastus lateralis biopsies by real-time PCR and Western blot analysis.

RESULTS: Although serum IGF-I was not significantly different (175 ± 10 ng/ml in CHF vs. 170 ± 12 ng/ml in HS, p = NS), local muscle IGF-I mRNA expression was reduced by 52% in CHF (6.7 ± 0.4 vs. 14.0 ± 0.9 arbitrary units in HS, p < 0.001). This was accompanied by an increase in IGF-I receptor mRNA expression (86.8 ± 5.4 in CHF vs. 23.1 ± 1.8 arbitrary units in HS, p < 0.001). Local IGF-I expression was significantly correlated with muscle cross-sectional area (R = 0.75, p = 0.01). Chronic heart failure patients with a body mass index of <25 kg/m² showed signs of peripheral growth hormone (GH) resistance, as indicated by elevated serum GH, and reduced IGF-I levels.

CONCLUSIONS: In CHF patients, muscle IGF-I expression is considerably reduced in the presence of normal serum IGF-I levels, possibly contributing to early loss of muscle mass. These findings are consistent with a potential role of IGF-I for skeletal muscle atrophy in CHF.

Abbreviations and Acronyms   CHF   chronic heart failure   CMP   cardiomyopathy   DCM   dilated cardiomyopathy   GH   growth hormone   HS   healthy subjects   IGF-I   insulin-like growth factor-I   IGFBP-3   insulin-like growth factor binding protein-3   IHD   ischemic heart disease   LVEF   left ventricular ejection fraction   mRNA   messenger ribonucleic acid   TNF-   tumor necrosis factor-   VO2max   maximal oxygen uptake

This article has been cited by other articles:

				L. H. Lund, P. Freda, J. J. Williams, J. J. LaManca, T. H. LeJemtel, and D. M. Mancini Growth hormone resistance in severe heart failure resolves after cardiac transplantation Eur J Heart Fail, May 1, 2009; 11(5): 525 - 528. [Abstract] [Full Text] [PDF]

				A. Bye, M. A. Hoydal, D. Catalucci, M. Langaas, O. J. Kemi, V. Beisvag, L. G. Koch, S. L. Britton, O. Ellingsen, and U. Wisloff Gene expression profiling of skeletal muscle in exercise-trained and sedentary rats with inborn high and low VO2max Physiol Genomics, November 12, 2008; 35(3): 213 - 221. [Abstract] [Full Text] [PDF]

				R. Aquilani, C. Opasich, A. Gualco, M. Verri, A. Testa, E. Pasini, S. Viglio, P. Iadarola, O. Pastoris, M. Dossena, et al. Adequate energy-protein intake is not enough to improve nutritional and metabolic status in muscle-depleted patients with chronic heart failure Eur J Heart Fail, November 1, 2008; 10(11): 1127 - 1135. [Abstract] [Full Text] [PDF]

				T. H. Le Jemtel, M. Padeletti, and S. Jelic Diagnostic and Therapeutic Challenges in Patients With Coexistent Chronic Obstructive Pulmonary Disease and Chronic Heart Failure J. Am. Coll. Cardiol., January 16, 2007; 49(2): 171 - 180. [Abstract] [Full Text] [PDF]

				P. Costelli, M. Muscaritoli, M. Bossola, F. Penna, P. Reffo, A. Bonetto, S. Busquets, G. Bonelli, F. J. Lopez-Soriano, G. B. Doglietto, et al. IGF-1 is downregulated in experimental cancer cachexia Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2006; 291(3): R674 - R683. [Abstract] [Full Text] [PDF]

				M. J. Toth, P. A. Ades, M. M. LeWinter, R. P. Tracy, and A. Tchernof Skeletal muscle myofibrillar mRNA expression in heart failure: relationship to local and circulating hormones J Appl Physiol, January 1, 2006; 100(1): 35 - 41. [Abstract] [Full Text] [PDF]

				P. C. Schulze, J. Fang, K. A. Kassik, J. Gannon, M. Cupesi, C. MacGillivray, R. T. Lee, and N. Rosenthal Transgenic Overexpression of Locally Acting Insulin-Like Growth Factor-1 Inhibits Ubiquitin-Mediated Muscle Atrophy in Chronic Left-Ventricular Dysfunction Circ. Res., September 2, 2005; 97(5): 418 - 426. [Abstract] [Full Text] [PDF]

				V. Adams, A. Linke, N. Krankel, S. Erbs, S. Gielen, S. Mobius-Winkler, J. F. Gummert, F. W. Mohr, G. Schuler, and R. Hambrecht Impact of Regular Physical Activity on the NAD(P)H Oxidase and Angiotensin Receptor System in Patients With Coronary Artery Disease Circulation, February 8, 2005; 111(5): 555 - 562. [Abstract] [Full Text] [PDF]

				J. P. Curtis, J. G. Selter, Y. Wang, S. S. Rathore, I. S. Jovin, F. Jadbabaie, M. Kosiborod, E. L. Portnay, S. I. Sokol, F. Bader, et al. The Obesity Paradox: Body Mass Index and Outcomes in Patients With Heart Failure Arch Intern Med, January 10, 2005; 165(1): 55 - 61. [Abstract] [Full Text] [PDF]

				M A Spruit, M J Thomeer, R Gosselink, T Troosters, A Kasran, A J T Debrock, M G Demedts, and M Decramer Skeletal muscle weakness in patients with sarcoidosis and its relationship with exercise intolerance and reduced health status Thorax, January 1, 2005; 60(1): 32 - 38. [Abstract] [Full Text] [PDF]

				L. Dalla Libera, B. Ravara, M. Volterrani, V. Gobbo, M. Della Barbera, A. Angelini, D. D. Betto, E. Germinario, and G. Vescovo Beneficial effects of GH/IGF-1 on skeletal muscle atrophy and function in experimental heart failure Am J Physiol Cell Physiol, January 1, 2004; 286(1): C138 - C144. [Abstract] [Full Text] [PDF]

				M A Spruit, R Gosselink, T Troosters, A Kasran, G Gayan-Ramirez, P Bogaerts, R Bouillon, and M Decramer Muscle force during an acute exacerbation in hospitalised patients with COPD and its relationship with CXCL8 and IGF-I Thorax, September 1, 2003; 58(9): 752 - 756. [Abstract] [Full Text] [PDF]

				R. Hambrecht, V. Adams, S. Erbs, A. Linke, N. Krankel, Y. Shu, Y. Baither, S. Gielen, H. Thiele, J.F. Gummert, et al. Regular Physical Activity Improves Endothelial Function in Patients With Coronary Artery Disease by Increasing Phosphorylation of Endothelial Nitric Oxide Synthase Circulation, July 1, 2003; 107(25): 3152 - 3158. [Abstract] [Full Text] [PDF]