Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension.

• Author: Nakanishi, Toshio.
• TeilnehmendeR: Baldwin, H. Scott.; Fineman, Jeffrey R.; Yamagishi, Hiroyuki.
• Place / Publishing House: Singapore : : Springer Singapore Pte. Limited,, 2020.; ©2020.
• Year of Publication: 2020
• Edition: 1st ed.
• Language: English
• Physical Description: 1 online resource (374 pages)

Table of Contents

Intro -- Preface -- Contents -- Part I: Basic Science of Pulmonary Development and Pulmonary Arterial Disease -- 1: Perspective for Part I -- 2: The Alveolar Stem Cell Niche of the Mammalian Lung -- 2.1 Introduction: The Alveolar Type 2 Epithelial Stem Cell Niche -- 2.2 Evidence for Heterogeneity in the AT2 Population -- 2.3 Signaling Pathways in the Stem Cell Niche -- 2.4 The Role of Immune Cells and Stromal Cells in Alveolar Repair and Regeneration -- 2.5 Future Directions and Clinical Implications -- References -- 3: Lung Development and Notch Signaling -- 3.1 Introduction -- 3.2 Morphogenesis and Epithelial Progenitors -- 3.3 Notch Signaling Controls Both Epithelial Cell Fates and Distributions -- 3.4 Development of NE Cell Clusters on Bifurcating Area of Branching Airways -- 3.5 Notch-Hes1 Signaling Is Required for Restricted Differentiation of Solitary NE Cells -- 3.6 Directional Migration of NE Cells Toward Bifurcation Points Creates Nodal NEBs -- References -- 4: Specialized Smooth Muscle Cell Progenitors in Pulmonary Hypertension -- 4.1 Introduction -- 4.2 Hypoxia-Induced Distal Pulmonary Arteriole SMCs Derive from Specialized SMC Progenitors -- 4.3 Stereotyped Program of Distal Muscularization -- 4.4 Monoclonal Expansion of SMCs in PH -- 4.5 Signaling Pathways Regulating Primed Cells -- 4.6 Future Direction and Clinical Implications -- References -- 5: Diverse Pharmacology of Prostacyclin Mimetics: Implications for Pulmonary Hypertension -- 5.1 Introduction -- 5.2 Development of Prostacyclin Mimetics and Their Diverse Pharmacology -- 5.3 Prostanoid Synthesis and Receptor Expression -- 5.3.1 Bronchial Smooth Muscle -- 5.3.2 Pulmonary Blood Vessels -- 5.3.2.1 Endothelium -- 5.3.2.2 Pulmonary Artery -- 5.3.2.3 Differential Prostanoid Expression in Distal Pulmonary Artery and Veins -- 5.3.2.4 Distal Pulmonary Veins.

5.3.3 Prostanoid Receptor Expression in PAH -- 5.3.3.1 Downregulation of IP Receptors in PAH -- 5.3.3.2 Robust Expression of EP2 and EP4 Receptors in PAH: Key Anti-Fibrotic Targets -- 5.3.3.3 EP3 Receptors May Contribute to Disease Pathology in PAH -- 5.3.3.4 Role of the Veins in PAH and Other Classified Groups of PH -- 5.4 BMPR2 and TGF-β Signalling in PAH and Impact of Prostacyclin Analogues -- 5.5 Regulation of TASK-1 By Prostacyclin Mimetics: Implications in PAH -- 5.6 Prostacyclin Effects on Vascular Remodelling In Vivo: Outstanding Issues -- 5.7 Future Work and Clinical Implications -- References -- 6: Endothelial-to-Mesenchymal Transition in Pulmonary Hypertension -- 6.1 Pulmonary Hypertension -- 6.2 Endothelial-to-Mesenchymal Transition -- 6.3 EndoMT in PAH Pathogenesis -- 6.3.1 EndoMT in PAH Vascular Remodeling -- 6.3.2 Molecular Pathways of EndoMT in PAH -- 6.4 Conclusion -- 6.5 Future Direction and Clinical Implications -- References -- 7: Extracellular Vesicles, MicroRNAs, and Pulmonary Hypertension -- 7.1 Extracellular Vesicles (EV) -- 7.2 EV in Pulmonary Hypertension (PH) -- 7.3 MicroRNA Transfer Through EV in PH -- 7.4 Future Direction and Clinical Implications -- References -- 8: Roles of Tbx4 in the Lung Mesenchyme for Airway and Vascular Development -- References -- 9: A lacZ Reporter Transgenic Mouse Line Revealing the Development of Pulmonary Artery -- References -- 10: Roles of Stem Cell Antigen-1 in the Pulmonary Endothelium -- References -- 11: Morphological Characterization of Pulmonary Microvascular Disease in Bronchopulmonary Dysplasia Caused by Hyperoxia in Newborn Mice -- References -- 12: Involvement of CXCR4 and Stem Cells in a Rat Model of Pulmonary Arterial Hypertension -- References.

13: Ca2+ Signal Through Inositol Trisphosphate Receptors for Cardiovascular Development and Pathophysiology of Pulmonary Arterial Hypertension -- References -- Part II: Abnormal Pulmonary Circulation in the Developing Lung and Heart -- 14: Perspective for Part II -- 14.1 Idiopathic Pulmonary Arterial Hypertension (IPAH) -- 14.2 Pulmonary Hypertension with Congenital Heart Disease -- 14.3 Pulmonary Circulation in Patients with Congenital Heart Disease -- References -- 15: Pathophysiology of Pulmonary Circulation in Congenital Heart Disease -- 15.1 Introduction -- 15.2 Comprehensive Assessment of Integrated Pulmonary Circulation -- 15.2.1 Physiologic Components of Pulmonary Circulation -- 15.2.2 Impedance Analysis -- 15.3 Pathophysiological Characteristics of Pulmonary Circulation in Congenital Heart Disease -- 15.3.1 Abnormal Resistance Is the Main Pathophysiology -- 15.3.2 Right Ventricular Function and Coupling to PA Load -- 15.3.3 Abnormalities of Compliance Is the Main Pathophysiology -- 15.3.4 Non-pulsatile Pulmonary Flow Is the Main Pathophysiology -- References -- 16: Development of Novel Therapies for Pulmonary Hypertension by Clinical Application of Basic Research -- 16.1 Introduction -- 16.2 Endothelial Function in the Development of PAH -- 16.3 PASMCs in the Development of PAH -- 16.4 Selenoprotein P in the Development of PAH -- 16.5 Conclusion -- References -- 17: Using Patient-Specific Induced Pluripotent Stem Cells to Understand and Treat Pulmonary Arterial Hypertension -- 17.1 Introduction -- 17.2 Patient-Specific iPSC-Derived Endothelial Cells to Model PAH -- 17.2.1 iPSC-EC Recapitulates Native Pulmonary Arterial Endothelial Cell (PAEC) -- 17.2.2 Patient-Specific Drug Response in IPSC-EC and PAEC -- 17.3 Modeling Reduced Penetrance of BMPR2 Mutation in PAH.

17.3.1 Preserved EC Function in Unaffected BMPR2 Mutation Carrier (UMC) -- 17.3.2 Preserved pP38 Signaling Pathway in Unaffected BMPR2 Mutation Carrier -- 17.4 Gene Editing in PAH IPSCs -- 17.4.1 Correction of the BMPR2 Mutation in PAH iPSCs -- 17.4.2 Generation of iPSC Line with BMPR2 Mutation -- 17.5 Future Directions and Clinical Implications -- References -- 18: Modeling Pulmonary Arterial Hypertension Using Induced Pluripotent Stem Cells -- 18.1 Heritable Pulmonary Arterial Hypertension -- 18.1.1 Insights into the Pathobiology of PAH -- 18.1.2 Reduced Penetrance of BMPR2 in PAH -- 18.2 Modeling Pulmonary Arterial Hypertension with Induced Pluripotent Stem Cells -- 18.2.1 Embryological Origins of the Pulmonary Vasculature -- 18.2.2 Current iPSC Models of PAH -- 18.3 Future Direction and Clinical Implications -- References -- 19: Dysfunction and Restoration of Endothelial Cell Communications in Pulmonary Arterial Hypertension: Therapeutic Implications -- 19.1 Introduction -- 19.2 Pulmonary Endothelial Dysfunction and the Pathobiology of PAH -- 19.3 Current Promising Strategies for Restoring Pulmonary Endothelial Dysfunction and Cell-Cell Communications -- 19.3.1 Restoring the Balance of Vasodilation and Vasoconstriction -- 19.3.2 Restitution of the Defective BMPR-2 Signaling System -- 19.3.3 Targeting Cell Proliferation and Cell accumulation -- 19.3.4 Restitution of an Adapted Extracellular Matrix (ECM) Remodeling -- 19.3.5 Targeting Metabolic Changes -- 19.3.6 Targeting the Vicious Cycle Between Endothelial Dysfunction and Immune Dysregulation -- 19.4 Future Directions and Clinical Implications -- References -- 20: Inflammatory Cytokines in the Pathogenesis of Pulmonary Arterial Hypertension -- 20.1 Background -- 20.2 IL-6 in the Pathogenesis of HPH -- 20.3 IL-21 in the Pathogenesis of HPH.

20.4 Increased Expression of IL-21 and M2 Macrophage Markers in the Lungs of IPAH Patients -- References -- 21: Genotypes and Phenotypes of Chinese Pediatric Patients with Idiopathic and Heritable Pulmonary Arterial Hypertension: Experiences from a Single Center -- 21.1 Introduction -- 21.2 Methods -- 21.3 Selection of Patients -- 21.4 Genetic Studies -- 21.5 Statistical Analysis -- 21.6 Results -- 21.6.1 Clinical Characteristics -- 21.6.2 Targeted Drug Therapy -- 21.6.3 Outcome of Patients -- 21.7 Discussion -- References -- 22: Fundamental Insight into Pulmonary Vascular Disease: Perspectives from Pediatric PAH in Japan -- 22.1 Early Detection and Early Treatment of PAH: Mechanistic Insights -- 22.2 Pathological Basis of Atypical CHD-PAH: Clinical and Mechanistic Implications -- 23: Risk Stratification in Paediatric Pulmonary Arterial Hypertension -- 23.1 Why Risk Stratify? -- 23.2 Multidimensional Risk Stratification -- 23.3 Factors to Consider in Multidimensional Risk Stratification of children with Pulmonary Arterial Hypertension -- 23.4 Cause of Pulmonary Hypertension -- 23.5 Vascular Burden -- 23.6 Ventricular Function -- 23.7 Impact on the Patient -- 23.8 Summary -- References -- 24: The Adaptive Right Ventricle in Eisenmenger Syndrome: Potential Therapeutic Targets for Pulmonary Hypertension? -- 24.1 Introduction -- 24.2 Improved Survival in Eisenmenger Syndrome -- 24.3 Preserved Fetal Morphology in Eisenmenger Syndrome -- 24.4 Fetal Phenotype in Ovine CHD Model -- 24.5 The Adaptive RV Response to Acute Afterload-RV Anrep Effect -- 24.6 Potential Mechanisms of RV Anrep Effect -- 24.7 Future Directions and Clinical Implications -- References -- 25: Impaired Right Coronary Vasodilator Function in Pulmonary Hypertensive Rats Assessed by In Vivo Synchrotron Microangiography -- References.

26: Relationship Between Mutations in ENG and ALK1 Genes and the Affected Organs in Hereditary Hemorrhagic Telangiectasia.