Signal Transduction and Cardiac Hypertrophy

Cellular signaling in cardiac muscle refers to the myriad of stimuli and responses that direct and control the physiological operation of this organ. Our understand­ ing of these complex signaling cascades has increased dramatically over the past few decades with the advent of molecular tools for their dissection. Moreover, this infor­ mation is beginning to provide tangible targets towards manipulating cardiac func­ tion in the setting of cardiovascular disease. The mechanisms and factors that regulate cardiac cell growth are of particular interest as both adaptive and maladaptive responses can occur during cardiac hypertrophy. Cardiac hypertrophy describes the increase in individual cardiac myocyte size that is accomplished through the series and/or parallel addition of sarcomeres. The ability of cardiac muscle to increase in size through hyperplasia becomes highly restricted or negligible shortly after birth. Consequently, the increase in heart size associated with development and growth of an individual occurs through hypertrophy. In response to a chronic increase in workload, cardiac muscle cells can dramatically increase in size to face their increasing contractile demands. While this plasticity is clearly a ben­ eficial response under many conditions, it can be highly deleterious and inappropri­ ate under others. For example, cardiac hypertrophy associated with endurance exercise clearly enhances athletic performance. In contrast, the hypertrophy associated with chronic hypertension, stenotic or regurgitant heart valves, or following a myocardial infarction often continues far beyond the period where this adaptive response is ben­ eficial.

Table of Contents:
I. Cardiac Adaptation and Remodeling.- 1. Molecular Changes of the Myocardium after Mechanical Circulatory Support.- 2. Reverse Molecular Remodeling of the Failing Human Heart Following Support with a Left Ventricular Assist Device.- 3. Stretch-Elicited Autocrine/Paracrine Mechanism in the Heart.- 4. L-Arginine at the Crossroads of Biochemical Pathways Involved in Myocardial Hypertrophy.- 5. Signal Transduction System in Human Aortic Smooth Muscle Cell Stimulated by Pure Pressure.- 6. Role of Mitochondrial KATP Channels in Improved Ischemic Tolerance of Chronically Hypoxic Adult and Immature Hearts.- 7. Ca2+–Dependent Signaling Pathways Through Calcineurin and Ca2+/Calmodulin–Dependent Protein Kinase in Development of Cardiac Hypertrophy.- 8. Calreticulin, Cardiac Development and Congenital Complete Heart Block in Children.- 9. Expression of Sodium-Calcium Exchanger Genes in Heart and Skeletal Muscle Development. Evidence for a Role of Adjacent Cells in Regulation of Transcription and Splicing.- 10. Na+/H+ Exchanger and Myocardial Hypertrophy.- II. Cardiac Signal Transduction.- 11. Role of the Electrogenic Na+/HCO3- Symport in the Heart.- 12. Modulation of Atrial Natriuretic Peptide (ANP)-C Receptor and Associated Signaling by Vasoactive Peptides.- 13. RAB3 Small GTP–Binding Proteins: Regulation by Calcium/Calmodulin.- 14. Novel Aspects of Mechanical Signaling in Cardiac Tissue.- 15. Caspase Activation in a Cardiac Cell-Free Model of Apoptosis.- 16. The Role of the Voltage-Sensitive Release Mechanism in Contraction of Normal and Diseased Heart.- 17. Role of AT1 Receptor Blockade in Reperfused Myocardial Infarction.- 18. Relation Between Intracellular Ca2+ Concentration and Contraction in Tetanized Myocyctes of Rat and Mouse.- 19. The Role of Hydrogen Peroxide as aSignaling Molecule.- 20. Localized Control of Oxidative Phosphorylation within Intracellular Energetic Units in Heart Cells: A Possible Solution of Some Old Problems.- 21. Role of High Molecular Weight Calmodulin Binding Protein in Cardiac Muscle.- 22. ?-Adrenergic Signaling in Chronic Heart Failure—Friend or Foe?.- 23. Compartmentation to Lipid Rafts as a Mechanism to Regulate ?-Adrenergic Receptor Signaling in Cardiomyocytes.- 24. Role of Renin-Angiotensin System in Phospholipase C-Mediated Signaling in Congestive Heart Failure.- 25. JAK/Stat Signaling in Cardiac Diseases.- III. Genetic Approaches to Investigative Cardiac Signal Transduction.- 26. Signaling Pathways Involved in the Stimulation of DNA Synthesis by Tumor Necrosis Factor and Lipopolysaccharide in Chick Embryo Cardiomyocytes.- 27. The Application of Genetic Mouse Models to Elucidate a Role for Fibroblast Growth Factor-2 in the Mammalian Cardiovascular System.- 28. Interaction of COUP-TF II With the Rat Carnitine Palmitoyltransferase I B Promoter in Neonatal Rat Cardiac Myocytes.- 29. Altered Expression of Conventional Calpains Influences Apoptosis.- 30. KLF5/BTEB2, a Krüppel-Like Transcription Factor, Regulates Smooth Muscle Phenotypic Modulation.- 31. Transgenic Manipulation of SERCA and PLB Levels and Their Effect on Cardiac Contractility.- 32. Expression of Vascular Endothelial Growth Factor and Hypoxia-Inducible Factor 1? in the Myocardium.- 33. Gene-Based Therapy of Advanced Heart Failure Secondary to the Disruption of Dystrophin-Related Proteom.- 34. Adaptation to Ischemia by In Vivo Exposure to Hyperoxia-Signalling Through Mitogen Activated Protein Kinases and Nuclear Factor Kappa B.- 35. The SERCA2 Gene: Genomic Organization and Promoter Characterization.