Myocardial Fas and Cytokine Expression in End‐Stage Heart Failure: Impact of LVAD Support

Left ventricular assist device (LVAD) support may facilitate myocardial recovery. We evaluated the impact of LVAD support on Fas expression in a cohort with end‐stage heart failure. Myocardial gene expression was assessed pre‐ and post‐LVAD by RNase protection assay and compared to control donor hearts. The expression of Fas is markedly elevated at the time of LVAD support and is tightly correlated with TNF expression. While interleukin (IL)‐6 was significantly reduced by LVAD support, the impact of support on Fas was highly variable and tightly linked to tumor necrosis factor (TNF). The role of Fas in predicting recovery after LVAD support requires further investigation.

[1]  M. Sack,et al.  Apoptosis: a pivotal event or an epiphenomenon in the pathophysiology of heart failure? , 2000, Heart.

[2]  H. Drexler,et al.  The cardiac Fas (APO-1/CD95) Receptor/Fas ligand system : relation to diastolic wall stress in volume-overload hypertrophy in vivo and activation of the transcription factor AP-1 in cardiac myocytes. , 2000, Circulation.

[3]  J. Pepper,et al.  Quantitative Myocardial Cytokine Expression and Activation of the Apoptotic Pathway in Patients Who Require Left Ventricular Assist Devices , 2001, Circulation.

[4]  R. Virmani,et al.  Apoptosis in myocytes in end-stage heart failure. , 1996, The New England journal of medicine.

[5]  B. Bozkurt,et al.  Results of Targeted Anti–Tumor Necrosis Factor Therapy With Etanercept (ENBREL) in Patients With Advanced Heart Failure , 2001, Circulation.

[6]  R. Holubkov,et al.  Myocardial expression of fas and recovery of left ventricular function in patients with recent-onset cardiomyopathy. , 2005, Journal of the American College of Cardiology.

[7]  K. Sliwa,et al.  Reduction in Fas/APO-1 plasma concentrations correlates with improvement in left ventricular function in patients with idiopathic dilated cardiomyopathy treated with pentoxifylline , 2000, Heart.

[8]  G. Noon,et al.  Decreased expression of tumor necrosis factor-alpha in failing human myocardium after mechanical circulatory support : A potential mechanism for cardiac recovery. , 1999, Circulation.

[9]  M. Cheitlin,et al.  Cardiac Improvement During Mechanical Circulatory Support: A Prospective Multicenter Study of the LVAD Working Group , 2008 .

[10]  R. Holubkov,et al.  Expression of proinflammatory cytokines in the failing human heart: comparison of recent-onset and end-stage congestive heart failure. , 2000, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[11]  G. MacGowan,et al.  Circulating interleukin-6 in severe heart failure. , 1997, The American journal of cardiology.

[12]  Douglas L Mann,et al.  Inflammatory mediators and the failing heart: past, present, and the foreseeable future. , 2002, Circulation research.

[13]  S. Yamaguchi,et al.  Elevated circulating levels and cardiac secretion of soluble Fas ligand in patients with congestive heart failure. , 1999, The American journal of cardiology.

[14]  P. Kang,et al.  Apoptosis and heart failure: A critical review of the literature. , 2000, Circulation research.

[15]  D. Darmer,et al.  Alternative splicing of the primary Fas transcript generating soluble Fas antagonists is suppressed in the failing human ventricular myocardium. , 1997, Biochemical and biophysical research communications.

[16]  B. Blaxall,et al.  Gene expression profile of the recovering human heart. , 2006, European heart journal.

[17]  A. Khaghani,et al.  Gene Profiling Changes in Cytoskeletal Proteins During Clinical Recovery After Left Ventricular–Assist Device Support , 2005, Circulation.

[18]  Magdi H Yacoub,et al.  Left ventricular assist device and drug therapy for the reversal of heart failure. , 2006, The New England journal of medicine.

[19]  D. Mann,et al.  Expression and functional significance of tumor necrosis factor receptors in human myocardium. , 1995, Circulation.

[20]  M. Oz,et al.  Implantable left ventricular assist devices: an evolving long-term cardiac replacement therapy. , 1997, Annals of surgery.

[21]  M. Yacoub,et al.  Molecular signature of recovery following combination left ventricular assist device (LVAD) support and pharmacologic therapy. , 2006, European heart journal.

[22]  M. Satoh,et al.  Inducible nitric oxide synthase and tumor necrosis factor-alpha in myocardium in human dilated cardiomyopathy. , 1997, Journal of the American College of Cardiology.

[23]  T. Myers,et al.  Myocardial tumor necrosis factor-alpha expression does not correlate with clinical indices of heart failure in patients on left ventricular assist device support. , 2001, The Annals of thoracic surgery.

[24]  H. Miller,et al.  Role of cytokines in heart failure. , 1998, American heart journal.

[25]  M. Bennett APOPTOSIS IN THE CARDIOVASCULAR SYSTEM , 2002, Heart.

[26]  Qin M. Chen,et al.  Apoptosis and Heart Failure , 2002, American journal of cardiovascular drugs : drugs, devices, and other interventions.

[27]  R. Ferrari,et al.  Neurohormones, Cytokines and Programmed Cell Death in Heart Failure: A New Paradigm for the Remodeling Heart , 2001, Cardiovascular Drugs and Therapy.

[28]  M C Oz,et al.  Long-term use of a left ventricular assist device for end-stage heart failure. , 2001, The New England journal of medicine.

[29]  O H Frazier,et al.  Cardiac Improvement During Mechanical Circulatory Support: A Prospective Multicenter Study of the LVAD Working Group , 2007, Circulation.

[30]  N. Bayley,et al.  Failure , 1890, The Hospital.

[31]  Marc A Simon,et al.  Myocardial Recovery Using Ventricular Assist Devices: Prevalence, Clinical Characteristics, and Outcomes , 2005, Circulation.