1;Preface;5 2;Contents;9 3;Contributors;11 4;Part I MicroRNA;16 4.1;An Overview of MicroRNA;17 4.1.1;1 Introduction;18 4.1.2;2 miRNA Biogenesis;19 4.1.3;3 Biological Functions of miRNAs;19 4.1.4;4 miRNAs in Human Disease;22 4.1.5;5 Summary;25 4.1.6;References;26 4.2;MicroRNAs and Their Potential;31 4.2.1;1 The Importance of Being miRNA;32 4.2.2;2 Post-Transcriptional Regulatory Mechanisms During Cardiac Hypertrophy;32 4.2.3;3 Post-Transcriptional Regulation by miRNA;32 4.2.4;4 Transcriptional and Post-Transcriptional Regulation of miRNA;37 4.2.5;5 The Mechanism of miRNA-Target Recognition;38 4.2.6;6 miRNA in Development and Disease;39 4.2.7;7 The Diagnostic and Prognostic Potential of miRNA;43 4.2.8;8 miRNA as Therapeutic Targets;44 4.2.9;9 Concluding Remarks;44 4.2.10;References;45 4.3;miRNAs and Their Emerging Role in Cardiac Hypertrophy;49 4.3.1;1 Introduction;50 4.3.2;2 Biology of miRNAs;50 4.3.3;3 miRNAs in Cardiovascular Development;54 4.3.4;4 miRNAs in the Hypertrophic Growth Response;58 4.3.5;5 Conclusions and Future Directions;62 4.3.6;References;62 4.4;MicroRNAs and the Control of Heart Pathophysiology;67 4.4.1;1 miRNA: Biogenesis and Mechanisms of Action;67 4.4.2;2 miRNAs and Muscle Development;73 4.4.3;3 miRNAs and Heart Pathophysiology;75 4.4.4;4 Conclusion and Future Prospects;79 4.4.5;References;79 4.5;MicroRNA Systems Biology;83 4.5.1;1 Introduction;84 4.5.2;2 miRNA Regulation of Cellular Signaling Networks;85 4.5.3;3 miRNA Regulation of Gene Regulatory Networks;91 4.5.4;4 miRNA Regulation of Metabolic Networks;93 4.5.5;5 miRNA Regulation of Protein Interaction Networks;94 4.5.6;6 miRNA Regulatory Network Motifs;95 4.5.7;7 Summary;98 4.5.8;References;98 5;Part II RNA Interference;101 5.1;Targeting Viral Heart Disease by RNA Interference;103 5.1.1;1 Introduction;103 5.1.2;2 Preclinical Results of Therapeutic Antiviral RNA Interference: Focus on CVB3- Associated Disease;106 5.1.3;3 Factors That Limit Early Efficacy of Antiviral RNA Interference;111 5.1.4;4 Factors That Limit Subsequent Efficacy of Antiviral RNA Interference;113 5.1.5;5 Conclusions and Future Prospects;116 5.1.6;References;117 5.2;Design of siRNAs and shRNAs for RNA Interference: Possible Clinical Applications;123 5.2.1;1 Introduction;124 5.2.2;2 Adverse Effects of Long dsRNAs;126 5.2.3;3 siRNA Structure and Design;127 5.2.4;4 shRNAs;134 5.2.5;5 Clinical Application;139 5.2.6;6 Concluding Remark;141 5.2.7;References;142 5.3;RNA Interference and MicroRNA Modulation for the Treatment of Cardiac Disorders;145 5.3.1;1 Introduction to RNA-Based and Gene Therapeutic Strategies;146 5.3.2;2 Key Issues of Current Vector Technologies;147 5.3.3;3 RNA Interference Targeting Early Pathogenic Steps in Cardiomyopathies;151 5.3.4;4 RNA Interference to Improve Cardiac Function in Advanced Heart Failure;165 5.3.5;5 Clinical Perspectives and Unanswered Questions;173 5.3.6;References;175 5.4;Cardiac Delivery of Nucleic Acids by Transcriptional and Transductional Targeting of Adeno- Associated Viral Vectors;181 5.4.1;1 Introduction;181 5.4.2;2 Vector Systems for Cardiac Nucleic Acid Transfer;183 5.4.3;3 Transductional Targeting of AAV Vectors for Cardiac Nucleic Acid Transfer;185 5.4.4;4 Transcriptional Targeting of AAV Vectors for Cardiac Nucleic Acid Transfer;187 5.4.5;5 Application Systems for Cardiac Gene Transfer;188 5.4.6;6 Perspective;191 5.4.7;References;191 6;Part III Ribozymes;197 6.1;Characterization of Hammerhead Ribozymes Potentially Suitable for the Treatment of Hyper- Proliferative Vascular Diseases;199 6.1.1;1 Introduction;200 6.1.2;2 Hammerhead Ribozyme;200 6.1.3;3 Potential Use of HRzs as Therapeutics for Artery Restenosis;211 6.1.4;4 HRzs and Small Interfering RNAs in the Cardiovascular Field;216 6.1.5;5 Conclusion;218 6.1.6;References;218 6.2;Applications of Ribozymes and Pyrrole - Imidazole Polyamides for Cardiovascular and Renal Diseases;223 6.2.1;1 Introduction;224 6.2.2;2 Ribozymes;225 6.2.3;3 Pyrrole-Imidazole (PI) Polyamides;236 6.2.4;4 Concl