Front Cover

Matrix Metalloproteinses and Tissue Remodeling in Health and Disease: Cardiovascular Remodeling

Copyright

Contents

Contributors

Preface

Chapter One: Biochemical and Biological Attributes of Matrix Metalloproteinases

1. Introduction

2. MMP Structure

3. Sources and Tissue Distribution of MMPs

4. MMP Activation

5. MMP Substrates

6. MMPs, ECM Degradation, and Tissue Remodeling

7. MMPs and Cell Signaling

7.1. MMPs and VSM Function

7.2. MMPs and Endothelial Cell Function

8. Special Attributes of Specific MMPs

8.1. Collagenases

8.1.1. MMP-1

8.1.2. MMP-8

8.1.3. MMP-13

8.1.4. MMP-18

8.2. Gelatinases

8.2.1. MMP-2

8.2.2. MMP-9

8.3. Stromelysins

8.3.1. MMP-3

8.3.2. MMP-10

8.3.3. MMP-11

8.4. Matrilysins

8.4.1. MMP-7

8.4.2. MMP-26

8.5. Membrane-Type MMPs

8.5.1. MMP-14

8.5.2. MMP-15

8.5.3. MMP-16

8.5.4. MMP-17

8.5.5. MMP-24

8.5.6. MMP-25

8.6. Other MMPs

8.6.1. MMP-12

8.6.2. MMP-19

8.6.3. MMP-20

8.6.4. MMP-21

8.6.5. MMP-22

8.6.6. MMP-23

8.6.7. MMP-27

8.6.8. MMP-28

9. MMP/TIMP Ratio

10. Concluding Remarks

Acknowledgments

References

Chapter Two: Matrix Metalloproteinases in Myocardial Infarction and Heart Failure

1. Introduction

2. MMPs as Biomarkers for Heart Failure

2.1. MMP-1

2.2. MMP-2

2.3. MMP-3

2.4. MMP-7

2.5. MMP-8

2.6. MMP-9

2.7. MMP-12

2.8. MMP-14

2.9. MMP-28

3. Clinical Use of MMP Inhibitors Post-MI

3.1. Direct Nonselective Inhibition

3.2. Direct Selective Inhibition

3.3. Indirect MMP Inhibition

3.4. General Considerations

4. Future Directions

5. Conclusion

Acknowledgments

References

Chapter Three: The Balance Between Metalloproteinases and TIMPs: Critical Regulator of Microvascular Endothelial Cell Fun ...

1. Introduction

2. Metalloproteinases

2.1. Matrix Metalloproteinases

2.1.1. Structure/Regulation

2.1.2. Function

2.2. A Disintegrin and Metalloproteinases

2.2.1. Structure/Regulation

2.2.2. Function

3. Tissue Inhibitor of Metalloproteinases

3.1. Structure/Regulation

3.2. Function

3.2.1. Metalloproteinase-Dependent TIMP Functions

3.2.2. Metalloproteinase-Independent TIMP Functions

4. Microvascular Endothelial Cells

4.1. Structure

4.1.1. Interactions of Adjacent EC

4.1.2. The Matrix of the Microvasculature

4.2. Function

4.2.1. MVEC Barrier Function

4.2.2. Other MVEC Functions

5. MVEC Dysfunction

5.1. Causes of MVEC Dysfunction

5.2. Features of MVEC Dysfunction

5.2.1. Mechanisms of MVEC Barrier Dysfunction

5.2.2. Regulation of Leukocyte-MVEC Interactions

6. Metalloproteinases in Endothelial Dysfunction

6.1. EC Metalloproteinase Expression

6.2. Function of Metalloproteinases in EC Dysfunction

7. TIMPs in Endothelial Dysfunction

7.1. EC TIMP Expression

7.2. TIMP Function in EC Dysfunction

8. Conclusion

8.1. Summary of Role of Metalloproteinase/TIMP Balance in MVEC Dysfunction

8.2. Therapeutic Potential of Manipulating the Metalloproteinase/TIMP Balance

References

Chapter Four: Matrix Metalloproteinases and Platelet Function

1. Platelets: Structure and Function

2. Expression of MMPs by Platelets and Megakaryocytes

2.1. Protein Expression

2.2. Protein Regulation

2.3. Transcripts for MMPs

2.4. MMPs and TIMPs Localization

2.5. Receptors Involved in MMP Activity on Platelets

3. Functions of MMPs in Platelets and Megakaryocytes

3.1. Regulation of MK and Platelet Function by MMPs and TIMPs

3.2. Modulation by Platelet MMPs of Other Cell Functions

3.3. Animal Models

3.4. Human Studies

4. Role of Platelet-Derived MMPs in Disease

4.1. Atherosclerosis

4.2. Inflammation

4.3. Tumor Growth and Metastasis

5. Conclusions

References

Chapter Five: Matrix Metalloproteinases and Leukocyte Activation

1. Introduction

2. Inflammation and Tissue Remodeling

3. Neutrophils, Macrophages, and Lymphocytes

3.1. Neutrophils

3.2. Macrophages

3.3. T Lymphocytes

4. MMP Regulation of Leukocyte Activity

4.1. Leukocyte Migration

4.1.1. Neutrophil Influx

4.1.2. Macrophage Influx

4.1.3. T Cells

4.1.4. Other Roles for MMPs in Leukocyte Migration

4.2. Cytokine Activity

4.3. Leukocyte Activation and Function

5. Concluding Remarks

References

Chapter Six: Evidence for the Involvement of Matrix-Degrading Metalloproteinases (MMPs) in Atherosclerosis

1. Atherosclerosis and Cardiovascular Disease

1.1. Healthy Arterial Anatomy

1.2. Atherosclerosis

2. Introduction to MMPs

2.1. MMP-1

2.2. MMP-2

2.3. MMP-3

2.4. MMP-7

2.5. MMP-8

2.6. MMP-9

2.7. MMP-10

2.8. MMP-11

2.9. MMP-12

2.10. MMP-13

2.11. MT-MMPs

2.12. MMP-14

2.13. MMP-16

3. TIMPs

3.1. TIMP-1

3.2. TIMP-2

3.3. TIMP-3

4. Conclusion

References

Chapter Seven: The Role Matrix Metalloproteinases in the Production of Aortic Aneurysm

1. Introduction

2. TAA and Dissection (TAD)

2.1. MMP-1

2.2. MMP-2

2.3. MMP-3 (Stromelysin) to MMP-8

2.4. MMP-9

2.5. MMP-12 to MMP-19

3. Abdominal Aortic Aneurysm (AAA)

3.1. MMP-1

3.2. MMP-2

3.3. MMP-3 (Stromelysin-1)

3.4. MMP-9

3.5. MMP-10

3.6. MMP-12

3.7. MMP-13

3.8. MMP-14 or Membrane Type-1 MMP (MT1-MMP)

4. Putative Signaling Pathways Involved in Aortic Aneurysm Development: Relationship to MMPs

5. Cigarettes and AAA Development

6. MMP Substrates and Pathogenesis of Aortic Aneurysm

7. Summary

References

Chapter Eight: Matrix Metalloproteinases in Remodeling of Lower Extremity Veins and Chronic Venous Disease

1. Introduction

2. Chronic Venous Disease (CVD)

3. Structural and Functional Abnormalities in VVs

4. MMP Levels in VVS

5. Potential MMP Inducers/Activators in VVs

5.1. Venous Hydrostatic Pressure and MMPs in VVs

5.2. Inflammation and MMPs in VVs

5.3. Hypoxia and MMPs in VVs

5.4. Other MMP Inducers/Activators in VVs

6. Mechanisms of MMP Actions in VVs

6.1. MMPs and ECM Abnormalities in VVs

6.2. MMPs and VSM Dysfunction in VVs

6.3. MMPs and Endothelium-Dependent Relaxation

7. Management of VVs

8. Potential Benefits of MMP Inhibitors in VVs

8.1. TIMPs and MMP/TIMP Ratio

8.2. Synthetic MMP Inhibitors

9. Concluding Remarks

Acknowledgments

References

Index

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