Color Plates 1–16 ……………………………………….. (Opposite page 112)
Part I. Methods
Chapter 1
Expression Profiling in Cardiovascular Disease Using Microarrays…….. 3
Branko Braam and Hans Bluyssen
1. General Introduction ……………………………………………………. 3
2. Technicalities in a Nutshell …………………………………………….. 4
3. Design …………………………………………………………………… 13
4. From Raw Data to Clean Data …………………………………………. 19
5. From Data to Interpretation ……………………………………………. 22
6. Applications in Cardiovascular Research ……………………………… 30
7. Conclusion ………………………………………………………………. 39
Chapter 2
Proteomics: State of the Art and Its Relevance for Gene Therapy………. 45
Sergiu Scobioala, Rainer Klocke, G ̈unter Michel, and Sigrid Nikol
1. Introduction ……………………………………………………………… 46
2. Technologies ……………………………………………………………. 47
3. Conclusions and Perspectives ………………………………………….. 60
xi
xii Contents
Chapter 3
Cardiovascular Proteomics…………………………………………………… 65
Rainer Klocke, Sergiu Scobioala, and Sigrid Nikol
1. Introduction ……………………………………………………………… 65
2. Proteomics in Basic Cardiovascular Research ………………………… 66
3. Modifications of Cardiovascular Proteomes under Chronic
Experimental or Pathological Conditions ……………………………… 67
4. Proteomics of Animal Models of Heart Diseases ……………………… 69
5. Conclusions and Perspectives ………………………………………….. 72
Chapter 4
Quantitative Real-Time PCR ………………………………………………… 75
J. P. G. Sluijter, G. Pasterkamp, and D. P. V. de Kleijn
1. Introduction ……………………………………………………………… 75
2. Nonspecific Fluorescent Quantification ……………………………….. 77
3. Specific Fluorescent Quantification ……………………………………. 79
4. Setting up a Quantitative PCR …………………………………………. 81
5. Concluding Remarks ……………………………………………………. 81
Chapter 5
New Technologies in Cardiovascular Research: Gene Therapy………….. 85
Marja Hedman, Mikko P. Turunen, and Seppo Yl ̈a-Herttuala
1. Introduction ……………………………………………………………… 85
2. Gene Transfer Routes …………………………………………………… 90
3. Animal Models for Studying Cardiovascular Diseases ……………….. 94
4. Summary ………………………………………………………………… 97
Chapter 6
The Role of Bioinformatics in Genomic Medicine …………………………. 103
A. H. C. van Kampen and A. J. G. Horrevoets
1. Introduction ……………………………………………………………… 103
2. Public Biological Databases ……………………………………………. 104
3. Development of (Statistical) Algorithms ………………………………. 108
4. Experimental Design for Genomics Experiments …………………….. 108
Contents xiii
5. Genomic Medicine ……………………………………………………… 110
6. Genomics and Bioinformatics in Cardiovascular
Research …………………………………………………………………. 111
Chapter 7
RNA Interference: Mechanisms and Therapeutic Applications…………. 121
Anne E. Lamers and Dominique P. V. de Kleijn
1. Introduction ……………………………………………………………… 121
2. RNAi: General Mechanisms ……………………………………………. 122
3. RNAi in Mammalian Cells …………………………………………….. 124
4. Considerations for the Design of RNAi Constructs …………………… 126
5. RNAi as a Therapeutic Tool ……………………………………………. 127
6. Conclusion ………………………………………………………………. 128
Part II. Applications
Chapter 8
Stem Cells and Cardiomyocytes………………………………………………133
Jennifer C. Moore, Teun P. de Boer, Marcel A. G. van der Heyden,
Leon G. J. Tertoolen, and Christine L. Mummery
1. Introduction ……………………………………………………………… 133
2. Signaling Pathways and Specification of Cardiac Cell Fate
by Extracellular Cues …………………………………………………… 136
3. Transcription Factors …………………………………………………… 139
4. Electrophysiology of Primary and ES-Derived Cardiomyocytes …….. 143
5. Perspectives for Transplantation ……………………………………….. 148
Chapter 9
Can Somatic Stem Cells Regenerate Myocardial Tissue? ………………… 157
Marie Jose Goumans, Anke Smits, Piet van Vliet, Simone Post,
Rutger J. Hassink, Pieter Stella, and Pieter A. Doevendans
1. Introduction ……………………………………………………………… 158
2. Somatic Stem Cells …………………………………………………….. 158
3. Mobilization of Endogenous Stem Cells ………………………………. 159
4. Injection of Stem Cells into the Injured Heart ………………………… 160
5. Somatic Stem Cells and Their Differentiation Capacity ……………… 162
xiv Contents
6. Cardiomyoblasts: Do They Exist? ……………………………………… 165
7. Conclusion ………………………………………………………………. 166
Chapter 10.
Gene Therapy for Angiogenesis……………………………………………… 171
Saurin R. Patel, Larry J. Diaz-Sandoval,
and Douglas W. Losordo
1. Introduction ……………………………………………………………… 171
2. Background ……………………………………………………………… 172
3. Scientific Rationale ……………………………………………………… 175
4. Safety Concerns …………………………………………………………. 192
5. Development Issues …………………………………………………….. 194
6. Summary ………………………………………………………………… 195
Chapter 11.
Tissue Engineering……………………………………………………………..207
Chris Denis Daly, Gordon R. Campbell, and Julie H. Campbell
1. Introduction ……………………………………………………………… 207
2. Vascular Grafts …………………………………………………………. 207
3. Heart Valves …………………………………………………………….. 212
4. Myocardium …………………………………………………………….. 214
5. Conclusion ………………………………………………………………. 217
Chapter 12.
Visualization of the Vulnerable Plaque ……………………………………… 221
Rob Krams, Johannes Schaar, Frank Helderman, Caroline Cheng,
Babak Mousavi Gourabi, L. C. A. Van Damme, D. Segers, Evelyn
Regar, Cornelis J. Slager, Pim J. de Feyter, Anton F. W. van der
Steen, and Patrick W. Serruys
1. Introduction ……………………………………………………………… 221
2. Angioscopy ……………………………………………………………… 222
3. Intravascular Coronary Ultrasound …………………………………….. 222
4. Intravascular Elastography/Palpography ………………………………. 223
5. Thermography …………………………………………………………… 224
6. Optical Coherence Tomography ……………………………………….. 226
7. Spectroscopic Techniques ………………………………………………. 227
Contents xv
8. Magnetic Resonance Imaging ………………………………………….. 228
9. Angus and Shear Stress …………………………………………………. 229
10. Conclusion ………………………………………………………………. 230
Index …………………………………………………………………………… 235
