Matrix Metalloproteinases in Health and Disease

The following sections are included:

• Dedication
• Acknowledgments
• Preface
• Contents

Exactly how proteinases act on their various protein substrates is a critical component in almost all aspects of normal physiology and disease pathology. Therefore, any discussion on matrix metalloproteinases (MMPs) must place these enzymes in the context of other classes of proteinases in order to fully understand and appreciate their contributions to biology. Many proteinases show exquisite specificity in targeting their protein substrate, whereas others are far more promiscuous, showing broad degradative activity against many substrates.

The following sections are included:

• The Age of Discovery
• Structure and Function of MMPs
• References

The following sections are included:

• Introduction
• Transcriptional Regulation
• Signal Transduction and the Induction of MMP Gene Expression
• Early Response Genes
• Novel Mechanisms Regulating MMP Transcription (Polymorphisms)
• “Targeted” Repression of MMP Transcription
• Posttranscriptional Mechanisms
• Epigenetic Regulation
• Summary
• References

The following sections are included:

• Introduction
• Recognizing New Substrates
• Pericellular Activities
• MMPs in Exosomes
• Intracellular Localization of MMPs
• Nuclear Localization
• MMPs as Signaling Molecules
• Conclusion
• References

The following sections are included:

• Introduction
• Experimental Systems and Normal Development
• “Trials and Tribulations” with MMPIs
• MMP Knockout Mice
• MMPs as “Good Guys”
• MMPs and Tissue Repair
• Conclusions
• References

“In rheumatology during my time, we had good people and discovered some interesting things. We were looking for how joints get destroyed in rheumatoid arthritis and bone disease, and we discovered the enzymes that are involved in breaking down the joint structure, collagenases. At the time it was a big discovery.”.

The following sections are included:

• Introduction
• When MMP Levels Increase, Cancer Risk Increases
• Polymorphisms
• Leveraging MMP Expression Changes as Biomarkers for Cancer
• Detecting and Monitoring Cancer via MMPs
• MMPs as Therapeutic Targets: Looking to the Future
• Summary
• References

The following sections are included:

• Introduction
• Atherosclerosis
• MMPs in Arterial Aneurysm Formation
• Myocardial Infarction
• Heart Failure
• MMPs and TIMPs as Prognostic Indicators of CVD
• Direct and Indirect MMP Inhibition
• References

The following sections are included:

• Introduction: Understanding the Failure of Early Clinical Trials: “Obstacles to the Therapeutic use of MMP Inhibitors ”
• Basic Biochemistry of MMPs and the History of MMPIs
• Novel Approaches to Designing MMPIs
• Strategies for Blocking MMP Gene Expression
• Conclusions
• References

The following sections are included:

• Introduction
• Neurobiology: A New Frontier and Paradigm for MMPs
• MMPs as Agents of Imaging and as Vehicles for Selective Drug-Delivery
• Actualizing the Power of MMPs as Prognostic Indicators in the Era of Precision Medicine
• Final Thoughts
• References

The following sections are included:

• Glossary
• Index