Cardiovascular Research
New Technologies,
Methods, and Applications
Cardiovascular Research
New Technologies,
Methods, and Applications
Edited by
Gerard Pasterkamp
University Medical Center Utrecht, The Netherlands
and
Dominique P. V. de Kleijn
University Medical Center
Utrecht, The Netherlands
Gerard Pasterkamp University Medical Center Experimental Cardiology Laboratory 3508 GA Utrecht
The Netherlands
Dominique P. V. de Kleijn University Medical Center Experimental Cardiology Laboratory 3584 CX Utrecht
The Netherlands
Library of Congress Control Number: 2005933093
ISBN-10: 0-387-23328-8; e-ISBN: 0-387-23329-6 Printed on acid-free paper.
ISBN-13: 978-0387-23328-4
C
2006 Springer Science+Business Media, Inc.
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List of Contributors
Hans Bluyssen Department of Nephrology and Hypertension, University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands
Branko Braam Department of Nephrology and Hypertension, University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands
Gordon R. Campbell Centre for Research in Vascular Biology, University of Queensland, Brisbane, QLD 4072, Australia
Julie H. Campbell Centre for Research in Vascular Biology, University of Queensland, Brisbane, QLD 4072, Australia
Caroline Cheng Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands
Chris Denis Daly Centre for Research in Vascular Biology, University of Queensland, Brisbane, QLD 4072, Australia
Teun P. de Boer Hubrecht Laboratory, Netherlands Institute of Developmen- tal Biology, Upsalalaan 8, 3584 CT, Utrecht, The Netherlands; and Depart- ment of Medical Physiology, University Medical Centre, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
Pim J. de Feyter Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands
D. P. V. de Kleijn Experimental Cardiology Laboratory, Heart Lung Center Utrecht, University Medical Center, Utrecht, The Netherlands; and In- teruniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands
Larry J. Diaz-Sandoval Divisions of Cardiovascular Medicine and Cardio- vascular Research, St. Elizabeth’s Medical Center of Boston, Tufts University School of Medicine, Boston, Massachusetts 02135
Pieter A. Doevendans Department of Cardiology, Interuniversity Cardiology Institute, Utrecht, The Netherlands
Marie Jose Goumans Department of Cardiology, Interuniversity Cardiology Institute, Utrecht, The Netherlands
v
vi Contributors
Babak Mousavi Gourabi Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands
Rutger J. Hassink Department of Cardiac Surgery, Heart Lung Center, Interuniversity Cardiology Institute, Utrecht, The Netherlands
Marja Hedman Department of Biotechnology and Molecular Medicine, A.I.
Virtanen Institute, University of Kuopio, Kuopio, Finland; and Department of Medicine, Kuopio University Hospital, Kuopio, Finland
Frank Helderman Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands
A. J. G. Horrevoets Department of Biochemistry, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
Rainer Klocke Department for Cardiology and Angiology, Westfälische Wilhelms University, M¨unster, Germany
Rob Krams Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands
Anne E. Lamers Experimental Cardiology Laboratory, University Medical Centre, Utrecht, The Netherlands
Douglas W. Losordo Divisions of Cardiovascular Medicine and Cardiovas- cular Research, St. Elizabeth’s Medical Center of Boston, Tufts University School of Medicine, Boston, Massachusetts 02135
G ¨unter Michel Department for Cardiology and Angiology, Westfälische Wilhelms University, M¨unster, Germany
Jennifer C. Moore Hubrecht Laboratory, Netherlands Institute of Develop- mental Biology, Upsalalaan 8, 3584 CT, Utrecht, The Netherlands
Christine L. Mummery Hubrecht Laboratory, Netherlands Institute of De- velopmental Biology, Upsalalaan 8, 3584 CT, Utrecht, The Netherlands Sigrid Nikol Department for Cardiology and Angiology, Westfälische
Wilhelms University, M¨unster, Germany
Gerard Pasterkamp Experimental Cardiology Laboratory, Heart Lung Center Utrecht, University Medical Center, Utrecht, The Netherlands; and Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands
Saurin R. Patel Divisions of Cardiovascular Medicine and Cardiovascular Research, St. Elizabeth’s Medical Center of Boston, Tufts University School of Medicine, Boston, Massachusetts 02135
Simone Post Department of Cardiology, Interuniversity Cardiology Institute, Utrecht, The Netherlands
Evelyn Regar Department of Cardiology, Thoraxcenter, Erasmus MC,
Rotterdam, The Netherlands
Contributors vii
Johannes Schaar Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands
Sergiu Scobioala Department for Cardiology and Angiology, Westfälische Wilhelms University, M¨unster, Germany; and Interdisciplinary Center for Clinical Research (IZKF), M¨unster, Germany
D. Segers Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands
Patrick W. Serruys Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands
Cornelis J. Slager Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands
J. P. G. Sluijter Experimental Cardiology Laboratory, Heart Lung Center Utrecht, University Medical Center, Utrecht, The Netherlands; and Interuni- versity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Nether- lands
Anke Smits Department of Cardiology, Interuniversity Cardiology Institute, Utrecht, The Netherlands
Pieter Stella Department of Cardiology, Interuniversity Cardiology Institute, Utrecht, The Netherlands
Leon G. J. Tertoolen Hubrecht Laboratory, Netherlands Institute of Devel- opmental Biology, Upsalalaan 8, 3584 CT, Utrecht, The Netherlands Mikko P. Turunen Department of Biotechnology and Molecular Medicine,
A.I. Virtanen Institute, University of Kuopio, Kuopio, Finland
L. C. A. Van Damme Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands
Marcel A. G. van der Heyden Hubrecht Laboratory, Netherlands Institute of Developmental Biology, Upsalalaan 8, 3584 CT, Utrecht, The Netherlands;
and Department of Medical Physiology, University Medical Centre, Univer- siteitsweg 100, 3584 CG, Utrecht, The Netherlands
Anton F. W. van der Steen Department of Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands
A. H. C. van Kampen Bioinformatics Laboratory, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
Piet van Vliet Department of Cardiology, Interuniversity Cardiology Institute, Utrecht, The Netherlands
Seppo Ylä-Herttuala Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute, University of Kuopio, Kuopio, Finland;
and Department of Medicine, Kuopio University Hospital, Kuopio, Finland
Preface
In the last decade, technical improvements have changed the inventory of many research laboratories. New techniques and discoveries continuously give rise to observations that result in the definition of new research objectives. In the past, re- search departments were clearly demarcated. Nowadays, technology that is shared by all lines of research stimulates convergence of research interests. This also ap- plies to cardiovascular research. Vascular occlusive disease is now core business for researchers employed by cardiology, vascular surgery, vascular medicine, ra- diology, cell biology, chemistry, physiology, and many other areas. Knowledge on actual research development is shared by researchers with different skills. It is sometimes difficult to acquire expertise when a researcher feels his experimental work could be improved by introducing a new research technique. In this book, the investigator will find an overview of recent developments that are relevant for research in general but cardiovascular research in particular. Genomics, pro- teomics, microarray, RNAi, stem cells, and progenitor cells are just some phrases that have become increasingly prevalent in literature in the last few years and that are recognized by many, but are fully understood by few. In this book, experts share the most appreciated new developments and techniques in cardiovascular research. We hope that this book will help the reader who is working in the field of cardiovascular research to understand and critically appreciate current research, and that it will help improve the quality of experimental work.
Dr G. Pasterkamp Dr DPV de Kleijn Utrecht, The Netherlands
ix
Contents
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
