The Pulmonary Endothelium

The Pulmonary Endothelium is a uniquely comprehensive compendium of our current knowledge of the pulmonary endothelium and is the first book dedicated specifically to the subject, offering insights into current and future approaches to management. The text provides the clinician with the most up-to-date information on one of the core physiological processes in airway disease and is an ideal point of reference for both postgraduates and professionals – specialist physicians in pulmonology and allergy and workers in biomedical and pharmaceutical research.

List of Contributors xi

Introduction xvii
Sharon Rounds and Norbert Voelkel

Section I: Normal Pulmonary Endothelium. Structure, Function, Cell Biology 1

1: Development of the Pulmonary Endothelium in Development of the Pulmonary Circulation: Vasculogenesis and Angiogenesis 3
Margaret A. Schwarz and Ondine B. Cleaver

2: Anatomy of the Pulmonary Endothelium 25
Radu V. Stan

3: Cadherins and Connexins in Pulmonary Endothelial Function 33
Kaushik Parthasarathi and Sadiqa K. Quadri

4: Pulmonary Endothelial Cell Interactions with the Extracellular Matrix 51
Katie L. Grinnell and Elizabeth O. Harrington

5: Pulmonary Endothelial Cell Calcium Signaling and Regulation of Lung Vascular Barrier Function 73
Nebojsa Knezevic, Mohammad Tauseef and Dolly Mehta

6: Pulmonary Endothelium and Nitric Oxide 89
Yunchao Su and Edward R. Block

7: Pulmonary Endothelial Cell Surface Metabolic Functions 105
Usamah S. Kayyali and Barry L. Fanburg

8: Cell Biology of Lung Endothelial Permeability 113
Guochang Hu and Richard D. Minshall

9: Lung Endothelial Phenotypes: Insights Derived from the Systematic Study of Calcium Channels 129
Donna L. Cioffi, Songwei Wu and Troy Stevens

10: Pulmonary Endothelial Interactions with Leukocytes and Platelets 143
Rosana Souza Rodrigues and Guy A. Zimmerman

11: Mesenchymal–Endothelial Interactions in the Control of Angiogenic, Inflammatory, and Fibrotic Responses in the Pulmonary Circulation 167
Kurt R. Stenmark, Evgenia V. Gerasimovskaya, Neil Davie and Maria Frid

12: Pulmonary Endothelium and Vasomotor Control 185
Nikki L. Jernigan, Benjimen R. Walker and Thomas C. Resta

13: Pulmonary Endothelial Progenitor Cells 203
Bernard Thébaud and Mervin C. Yoder

14: Bronchial Vasculature: The Other Pulmonary Circulation 217
Elizabeth Wagner

15: Mapping Protein Expression on Pulmonary Vascular Endothelium 229
Kerri A. Massey and Jan E. Schnitzer

Section II: Mechanisms and Consequences of Pulmonary Endothelial Cell Injury 241

16: Pulmonary Endothelial Cell Death: Implications for Lung Disease Pathogenesis 243
Qing Lu and Sharon Rounds

17: Oxidant-Mediated Signaling and Injury in Pulmonary Endothelium 261
Kenneth E. Chapman, Shampa Chatterjee and Aron B. Fisher

18: Hypoxia and the Pulmonary Endothelium 287
Matthew Jankowich, Gaurav Choudhary and Sharon Rounds

19: Viral Infection and Pulmonary Endothelial Cells 303
Norbert F. Voelkel

20: Effects of Pressure and Flow on the Pulmonary Endothelium 309
Wolfgang M. Kuebler

21: Therapeutic Strategies to Limit Lung Endothelial Cell Permeability 337
Rachel K. Wolfson, Gabriel Lang, Jeff Jacobson and Joe G. N. Garcia

22: Targeted Delivery of Biotherapeutics to the Pulmonary Endothelium 355
Vladimir R. Muzykantov

Section III: Pulmonary Endothelium In Disease 379

23: Endothelial Regulation of the Pulmonary Circulation in the Fetus and Newborn 381
Yuansheng Gao and J. Usha Raj

24: Genetic Insights into Endothelial Barrier Regulation in the Acutely Inflamed Lung 399
Sumegha Mitra, Daniel Turner Lloveras, Shwu-Fan Ma and Joe G. N. Garcia

25: Interactions of Pulmonary Endothelial Cells with Immune Cells and Platelets: Implications for Disease Pathogenesis 417
Mark R. Nicolls, Rasa Tamosiuniene, Ashok N. Babu and Norbert F. Voelkel

26: Role of the Endothelium in Emphysema: Emphysema – A Lung Microvascular Disease 437
Norbert F. Voelkel and Ramesh Natarajan

27: Pulmonary Endothelium and Pulmonary Hypertension 449
Rubin M. Tuder and Serpil C. Erzurum

28: Collagen Vascular Diseases and Pulmonary Endothelium 461
Pradeep R. Rai and Carlyne D. Cool

29: Pulmonary Endothelium in Thromboembolism 471
Irene M. Lang

30: Pulmonary Endothelium and Malignancies 485
Abu-Bakr Al-Mehdi

Epilogue
Norbert F. Voelkel

Index 495

Norbert Voelkel and Sharon Rounds are the authors of The Pulmonary Endothelium: Function in Health and Disease, published by Wiley. The pulmonary endothelium interacts with both blood and underlying vascular smooth muscle.

As well as being critical for gas exchange, the lung endothelium is now implicated in the modulation of a variety of processes, such as inflammation, thrombosis, vasoconstriction, and vascular permeability. Our understanding of the pulmonary endothelium has increased enormously in recent years, particularly its role in several diseases, including pulmonary hypertension, emphysema, acute respiratory distress syndrome, and cancer.

Research in many fields continues to elucidate how the pulmonary endothelium contributes to the etiology and pathophysiology of lung disease and to identify possible therapeutic strategies. This book clearly presents the current body of knowledge and explores how this knowledge may be applied to increase our understanding of disease and develop new types of treatment. Above all, it aims to improve the outcomes of acute and chronic lung diseases.

The book is divided into three sections. The first describes the normal pulmonary endothelium, including development, structure, cell biology, signalling, function, heterogeneity, interactions with circulating cells and mesenchymal cells, and the endothelium of the bronchial circulation. The second section deals with mechanisms and consequences of pulmonary endothelial cell injury, ranging from effects on endothelial cells to organ injury, including protection against lung permeability and drug targeting to pulmonary endothelium. The third section focuses on the pulmonary endothelium in disease.

• Describes and discusses the lung endothelium as the first and principal locus of blood-born information processing
• Reviews maintenance of normal lung vascular tone and modulation of vasoconstriction
• Discusses the lung endothelium in modulation of pulmonary vascular remodelling
• Highlights recent work on the important role of the lung endothelium in the pathogenesis of lung diseases

The Pulmonary Endothelium provides specialist physicians and clinical researchers in pulmonology, critical care, and allergy with the most up to date information on core physiological processes in lung disease, and offers insights into current and future approaches to management.