This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: j.jacc.2006.07.007v1 48/9_Suppl_A/A56    most recent 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 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 Hilfiker-Kleiner, D. Articles by Drexler, H. Search for Related Content PubMed Articles by Hilfiker-Kleiner, D. Articles by Drexler, H.

STATE-OF-THE-ART PAPER

Molecular Mechanisms in Heart Failure

Focus on Cardiac Hypertrophy, Inflammation, Angiogenesis, and Apoptosis

Departments of Cardiology and Angiology, Hannover Medical School, Hannover, Germany

Manuscript received December 8, 2005; revised manuscript received May 25, 2006, accepted June 6, 2006.

^_* Reprint requests and correspondence: Dr. Helmut Drexler, Department of Cardiology and Angiology, Medizinische Hochschule Hannover, Carl-Neuberg Strasse 1, 30625 Hannover, Germany. (Email: drexler.helmut{at}mh-hannover.de).

Heart failure is a final common pathway in cardiovascular disease, as a result of sustained pressure overload (i.e., hypertension), myocardial ischemia or infarction, volume overload (i.e., mitral regurgitation), or inherited and acquired cardiomyopathies. Heart failure is a major health care burden, and despite significant therapeutic advances, morbidity and mortality in heart failure remain unacceptably high. Therefore, novel insights into pathophysiology and molecular mechanisms of heart failure are required to develop novel therapeutic approaches. In this review we highlight several advances in the understanding of molecular pathways involved in cardiac hypertrophy, inflammatory signaling (i.e., tumor necrosis factor-, interleukin-6), and oxidant stress that may play a key role in altering transcriptional regulatory networks regulating adaptation or maladaptation, and consequently, the transition to overt heart failure. In this respect we focus on paracrine mechanisms (vascular endothelial growth factor, CCN1) and intracellular signaling (interleukin-6–glycoprotein 130–signal transducer and activator of transcription-3). In addition, we highlight the impact of current treatment options on these molecular pathways and their potential impact on progression of heart failure.

Abbreviations and Acronyms   Akt = protein kinase B   ERK = extracellular signal-regulated kinases   gp130 = glycoprotein 130   GSK = glycogen synthase kinase   IL-6 = interleukin-6   JAK = Janus kinase   LIF = leukemia inhibitory factor   LV = left ventricle/ventricular   MHC = myosin heavy chain   MLP = muscle limb protein   NF-kappaB = nuclear factor kappaB   NO = nitric oxide   PI3-K = phosphatidylinositol 3-kinase   ROS = reactive oxygen species   STAT3 = signal transducer and activator of transcription   TNF- = tumor necrosis factor-   VEGF = vascular endothelial growth factor

This article has been cited by other articles:

				L. Chen, Q. Gong, J. P. Stice, and A. A. Knowlton Mitochondrial OPA1, apoptosis, and heart failure Cardiovasc Res, October 1, 2009; 84(1): 91 - 99. [Abstract] [Full Text] [PDF]

				C. Hu, A. Dandapat, L. Sun, M. R. Marwali, N. Inoue, F. Sugawara, K. Inoue, Y. Kawase, K.-i. Jishage, H. Suzuki, et al. Modulation of Angiotensin II-Mediated Hypertension and Cardiac Remodeling by Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Deletion Hypertension, September 1, 2008; 52(3): 556 - 562. [Abstract] [Full Text] [PDF]

				S. M. Zick, B. Gillespie, and K. D. Aaronson The effect of Crataegus oxycantha special extract WS 1442 on clinical progression in patients with mild to moderate symptoms of heart failure Eur J Heart Fail, June 1, 2008; 10(6): 587 - 593. [Abstract] [Full Text] [PDF]

				E. D. Abel, S. E. Litwin, and G. Sweeney Cardiac Remodeling in Obesity Physiol Rev, April 1, 2008; 88(2): 389 - 419. [Abstract] [Full Text] [PDF]

				C. P. Dahl, L. Gullestad, B. Fevang, A. M. Holm, L. Landro, L. E. Vinge, A. E. Fiane, W. J. Sandberg, K. Otterdal, S. S. Froland, et al. Increased expression of LIGHT/TNFSF14 and its receptors in experimental and clinical heart failure Eur J Heart Fail, April 1, 2008; 10(4): 352 - 359. [Abstract] [Full Text] [PDF]

				P. Pokreisz, G. Marsboom, and S. Janssens Pressure overload-induced right ventricular dysfunction and remodelling in experimental pulmonary hypertension: the right heart revisited Eur. Heart J. Suppl., December 1, 2007; 9(suppl_H): H75 - H84. [Abstract] [Full Text] [PDF]