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Vascular Pharmacology: Smooth Muscle

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Contents

Contributors

Preface

Chapter One: Nanojunctions of the Sarcoplasmic Reticulum Deliver Site- and Function-Specific Calcium Signaling in Vascula ...

1. Introduction

2. What Defines a Nanojunction?

2.1. The PM-SR Nanojunctions of Vascular Smooth Muscles

2.1.1. Refilling of the SR

2.1.2. Emptying of the SR

2.2. Multiple Releasable Pools of SR Ca2+

2.2.1. SERCA2a, RyR3, and RyR2 Are Resident in the Deep SR of Pulmonary Arterial Myocytes and Underpin Vasoconstriction

2.2.2. Can Ca2+ Be Locked Within Junctional Complexes?

2.2.3. Multiple Paths to Smooth Muscle Contraction

2.3. Lysosome-SR Nanojunctions

2.3.1. Lysosome-SR Junctions Form a Trigger Zone for Ca2+ Signaling by NAADP

2.3.2. Lysosomes Colocalize With RyR Subtype 3 to Form a Trigger Zone for Ca2+ Signaling in Pulmonary Arterial Smooth Muscle

2.3.3. Why Might RyR3 Be Targeted to Lysosome-SR Junctions?

2.3.4. How May Ca2+ Signals Propagate Away From Lysosome-SR Junctions to the Wider Cell If RyR3 Is Restricted to the Peri ...

2.3.5. Tissue Specificity and Plasticity of Lysosome-SR Junctions

2.4. Mitochondria-SR Nanojunctions

2.5. Nuclear Invaginations May Provide a Nanodomain Within Which Ca2+ Signals May Be Generated to Modulate Gene Expression

2.5.1. How Might Nuclear Invaginations Coordinate Ca2+ Signals and Thus Gene Expression via Their Incorporated Cytoplasmi ...

2.6. Could Nanojunctions of the SR Support Network Activity?

2.6.1. Unloading of the SR, Loss of Function, and Vasodilation

2.6.2. Refilling of the SR and Gain of Function

2.7. Junctional Reorganization During the Switch From a Contractile to a Migratory and Proliferative Smooth Muscle Phenotype

2.8. Couplons and Ca2+ Exchange Across and Between Cytoplasmic Nanodomains

3. Conclusion

Conflict of Interest

Acknowledgments

References

Chapter Two: Calcium Channels in Vascular Smooth Muscle

1. Introduction

2. Plasmalemmal Ca2+-Permeable Channels

2.1. Voltage-Dependent Calcium Channels

2.1.1. L-Type CaV1.2 Channels

2.1.2. T-Type Ca2+ Channels

2.2. TRP Channels

2.2.1. TRPV1

2.2.2. TRPV2

2.2.3. TRPV4

2.2.4. TRPC1

2.2.5. TRPC3

2.2.6. TRPC4

2.2.7. TRPC5

2.2.8. TRPC6

2.2.9. TRPM4

2.2.10. TRPP2

2.2.11. Intracellular TRP Channels

2.3. Orai and STIM

3. SR Ca2+ Channels

3.1. Ryanodine Receptors

3.2. Inositol-1,4,5,-Trisphosphate Receptors

4. Mitochondrial Ca2+ Channels

5. Conclusion

Conflict of Interest

Acknowledgments

References

Chapter Three: Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth

1. Introduction

2. Potassium Channels and Regulation of VSM Contraction

2.1. Setting the Stage

2.2. BKCa Channels and VSM Contraction

2.3. Diseases and VSM BKCa Channels

2.4. KV Channels and VSM Contraction

2.5. Disease and VSM KV Channels

2.6. KATP Channels and VSM Contraction

2.7. Disease and VSM KATP Channels

2.8. KIR Channels and VSM Contraction

2.9. Diseases and VSM KIR Channels

3. K+ Channels and VSM Proliferation

3.1. KCa3.1 and VSM Proliferation

3.2. KV Channels and VSM Proliferation

4. Conclusion

Conflict of Interest

Acknowledgments

References

Chapter Four: Sodium-Calcium Exchanger in Pig Coronary Artery

1. Introduction

2. NCX in Coronary Artery Smooth Muscle

3. NCX in SMC

4. Functional Coupling of NCX and SER in SMC

5. Colocalization of NCX1 and SERCA2 in SMC

6. Effect of Thapsigargin on Colocalization of NCX1 and SERCA2 in SMC

7. Comparison of NCX in Coronary Artery SMC and EC

8. Conclusion

Conflict of Interest

Acknowledgments

References

Chapter Five: Ca2+/Calmodulin-Dependent Protein Kinase II in Vascular Smooth Muscle

1. Introduction

2. CaMKII Structure and Expression in VSM

3. CaMKII Activation in VSM

3.1. Thr287 Autophosphorylation and Autonomous Activity

3.2. CaMKII Oxidation and Nitrosylation

4. CaMKII Function in VSM

4.1. Differentiated VSM Contractile Function

4.2. Synthetic Phenotype Function

4.2.1. VSM Phenotype Switching

4.2.2. CaMKII and Gene Transcription

4.2.3. CaMKII Cross Talk with ERK1/2 and Tyrosine Kinases in VSM

4.2.4. CaMKII Regulation of VSM Cell Motility

4.2.5. CaMKII Regulation of VSM Cell Proliferation

4.3. CaMKII Isozymes in Vascular Remodeling In Vivo

5. Conclusion

Conflict of Interest

References

Chapter Six: Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders

1. Introduction

2. PKC Structure and Isoforms

3. PKC Distribution and Translocation

4. PKC Phosphorylation

5. PKC Activators

6. PKC Substrates

7. PKC Inhibitors

8. Vascular Effects of PKC

8.1. PKC and VSM Contraction

8.2. PKC, Ion Channels, and [Ca2+]i

8.3. PKC, Ion Pumps and Cotransporters, and [Ca2+]i

8.4. PKC and Ca2+-Sensitization of Contractile Proteins

8.5. PKC and Cytoskeletal Proteins

8.6. PKC-Dependent Signaling Cascades

8.7. PKC and Vasodilation

9. Physiological Changes in PKC

9.1. Age-Related Changes in PKC

9.2. Sex Differences in PKC

9.3. Pregnancy-Related Changes in PKC

10. PKC in Vascular Injury and Disease

10.1. PKC, VSM Growth, and Angiogenesis/Vasculogenesis

10.2. PKC and VSM Apoptosis

10.3. PKC and Vascular Inflammation

10.4. PKC and Vascular Restenosis

10.5. PKC and Oxidative Stress

10.6. PKC and Ischemia/Reperfusion Injury

10.7. PKC and Coronary Artery Disease

10.8. PKC and Hypertension

10.9. PKC and Diabetic Vasculopathy

10.10. PKC and Atherosclerosis

11. Conclusion

Conflict of Interest

Acknowledgments

References

Chapter Seven: Rho-Mancing to Sensitize Calcium Signaling for Contraction in the Vasculature: Role of Rho Kinase

1. Introduction

2. RhoA/Rho Kinase Structure and Expression

3. Rho Kinase Function

4. Regulation of RhoA/Rho Kinase Activity via Posttranslational Modifications

5. RhoA/Rho Kinase-Mediated Ca2+ Sensitization in Vascular Disease and Rho Kinase Inhibitors: Focus on Hypertension

6. Conclusion

Conflict of Interest

References

Chapter Eight: Vascular Cells in Blood Vessel Wall Development and Disease

1. Introduction

2. Blood Vessel Development

2.1. Endothelial Cells

2.2. Smooth Muscle Cells

2.3. Pericytes

2.4. Adventitial Cells

2.5. Vascular ECM

3. Cardiovascular Diseases

3.1. Supravalvular Aortic Stenosis

3.2. Aortic Aneurysms

3.3. Pulmonary Hypertension

3.4. Atherosclerosis

3.5. Germinal Matrix Hemorrhage

4. Conclusion

Conflict of Interest

References

Chapter Nine: Notch Signaling in Vascular Smooth Muscle Cells

1. Introduction

2. The Notch Signaling Pathway

2.1. The Canonical Notch Signaling Pathway

2.2. Interaction with Other Signaling Pathways and Noncanonical Signaling

2.2.1. Platelet-Derived Growth Factor B

2.2.2. Transforming Growth Factor β

2.2.3. Mitogen-Activated Protein Kinase

2.2.4. Wingless-Related Integration Site

3. Notch Signaling in VSMC Development

3.1. Constructing a Vessel Wall

3.2. Arterial-Venous Specification

4. Notch Signaling and VSMC Phenotype

4.1. Differentiation

4.2. Proliferation

4.3. Survival

4.4. Extracellular Matrix Synthesis

4.5. Migration

5. Notch Signaling in Vascular Disease

5.1. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

5.2. Patent Ductus Arteriosus

5.3. Alagille Syndrome

5.4. Pulmonary Arterial Hypertension

5.5. Infantile Myofibromatosis

5.6. Vascular Injury

6. Conclusion

Conflict of Interest

Acknowledgments

References

Chapter Ten: Smooth Muscle Phenotypic Diversity: Effect on Vascular Function and Drug Responses

1. Introduction

2. Brief Review of the Players in VSM Contractile Function

3. Diversity Within the Vascular System

4. Agonist-Mediated Vasoconstriction and Its Antagonism

4.1. Vasoconstriction

4.2. Unresolved Questions

4.3. Clinical Significance

5. Signaling-Mediated Vasodilation and Its Agonism

5.1. NO-Mediated Vasodilation and Specificity

5.1.1. Calcium Sensitivity and MP

5.1.2. Calcium Flux and IRAG

5.2. Other Components of Vasorelaxant Signaling

5.3. Unresolved Questions

5.4. Clinical Significance

6. Calcium Flux and Its Inhibition

6.1. LTCC

6.2. NCX

7. Diversity Within Human Populations

7.1. Human Diversity and Vascular Function

7.2. Diversity and VSM Drug Responses

7.3. Newer Methodology: iPS (Induced Pluripotent Stem) Cells

8. Conclusion

Conflict of Interest

Acknowledgment

References

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