The Cardiac Lymphatic System

The Cardiac Lymphatic System

Ganga Karunamuni Editor The Cardiac Lymphatic System An Overview

Editor Ganga Karunamuni Department of Pediatrics Case Western Reserve University Cleveland, OH, USA ISBN 978-1-4614-6773-1 ISBN 978-1-4614-6774-8 (ebook) DOI 10.1007/978-1-4614-6774-8 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2013935496 Springer Science+Business Media New York 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher's location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)

Preface The heart is invested with a complex, intertwining network of blood and lymphatic vessels which, respectively, provide the cardiac tissue with oxygen and nutrients and eliminate excess fluid from the interstitium. The coronary blood vessels have been the focus of much investigation in the past few decades. On the other hand, the literature regarding the cardiac lymphatic vessels remains sparse, despite their important role in maintaining normal heart function. For example, in the event of lymphatic blockage, destruction, or dysfunction, cardiac edema as well as fibrosis and inflammation can be observed in the affected regions of the heart. With this in mind, a better understanding of the cardiac lymphatic network and its ability to regulate fluid homeostasis within the heart could give us insight into developing therapies for the alleviation of several cardiac pathological conditions. This book aims to provide in-depth coverage of the cardiac lymphatic vessels and the essential nature of their patterning and development in the heart tissue. The volume is organized into three parts: the anatomy of the cardiac lymphatic system (Chaps. 1 and 2 ), the cardiac lymphatics and heart disease (Chaps. 3, 4, 5, 6, and 7 ), and cardiac lymphatic signaling (Chaps. 8, 9, 10, and 11 ). The first two chapters illustrate the general anatomy of the lymphatic vessels existing within the epicardium, myocardium, and endocardium of the heart. Chapter 3 investigates the role of the lymphatics in the development of congenital heart disease, while Chap. 4 reviews their function in a variety of cardiac pathologies including myocardial infarction and congestive heart failure. Chapter 5 covers the valvular lymphatics under both normal and disease conditions. Chapter 6 discusses some therapeutic applications targeting the cardiac lymphatics during heart disease as well as the limitations of such practices, and Chap. 7 outlines the various imaging modalities that are available for the visualization of the lymphatic vasculature. Chapters 8, 9, and 10 highlight certain crucial signaling pathways (Tie, VEGF, and HIF, respectively) that are involved in the regulation of the cardiac lymphatics. Finally, Chap. 11 delves into the potential of the epicardium to act as a source of stem cells for damaged or regenerating lymphatic vessels. The volume will be useful to a broad audience interested in cardiovascular medicine and physiology, including clinicians, students, and researchers in the fields of v

vi Preface developmental biology, cardiology, and applied anatomy. The groundwork in this book will be able to provide readers with vital information on the crucial role played by the cardiac lymphatic vessels in preserving normal heart function. My primary thanks go to the contributors, key leaders in the field, without whom this book would not have been possible. Their time and enthusiasm are greatly appreciated. I would also like to thank my family, especially my husband Matthew Krock, for their unwavering love and support during this project. Cleveland, OH, USA Ganga Karunamuni, PhD

Contents Part I Anatomy of the Cardiac Lymphatic System 1 A General Outline of the Cardiac Lymphatic System... 3 Marios Loukas, Sameer Shah, Shivayogi Bhusnurmath, Bharti Shivayogi Bhusnurmath, and R. Shane Tubbs 2 Development and Patterning of the Cardiac Lymphatic Network... 17 Jörg Wilting and Jörg Männer Part II The Cardiac Lymphatics and Heart Disease 3 The Link Between Lymphatic Obstruction and Congenital Heart Disease... 35 Manish Bansal 4 The Role of Lymphatics in Atherogenesis, Myocardial Infarction, Congestive Heart Failure, and Cardiac Transplantation... 45 Shin Lin and Stanley G. Rockson 5 The Lymphatics in Normal and Pathological Heart Valves... 63 Ivana Kholová, Galina Dragneva, and Seppo Ylä-Herttuala 6 Therapeutic Applications Targeting the Cardiac Lymphatics in Heart Disease... 73 Jae-Hyeong Park and Jin-Ok Jeong 7 Imaging the Lymphatic System in Heart Transplantation and Its Immunological Implications... 87 Kathryn Brown, Lindsey A. Edwards, and Wilson Wong vii

viii Contents Part III Cardiac Lymphatic Signaling 8 Tie Receptor Signaling in Cardiac Lymphangiogenesis... 107 Xianghu Qu and H. Scott Baldwin 9 VEGF Receptor Signaling in the Cardiac Lymphatics... 125 Alexey Dashkevich, Karl B. Lemström, and Antti I. Nykänen 10 Hypoxia and the Cardiac Lymphatic System... 145 Todd R. Wuest and P. Charles Lin 11 The Potential of the Epicardium to Act as a Source of Lymphatic Cells... 161 Linda Klotz and Paul Riley Index... 183

Contributors H. Scott Baldwin Division of Cardiology, Vanderbilt Children s Hospital, Nashville, TN, USA Manish Bansal Department of Pediatrics/Pediatric Cardiology, UH Rainbow Babies and Children s Hospital, Case Western Reserve University, Cleveland, OH, USA Bharti Shivayogi Bhusnurmath Department of Pathology, St. George s University School of Medicine, St. George, Grenada Shivayogi Bhusnurmath Department of Pathology, St. George s University School of Medicine, St. George, Grenada Kathryn Brown MRC Center for Transplantation, King s College London School of Medicine at Guy s, King s and St. Thomas Hospitals, London, UK Alexey Dashkevich Transplantation Laboratory, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland Galina Dragneva Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland Lindsey A. Edwards MRC Center for Transplantation, King s College London School of Medicine at Guy s, King s and St. Thomas Hospitals, London, UK Jin-Ok Jeong Department of Internal Medicine, Chungnam National University Hospital, Regional Cardiovascular Center, Daejeon, Korea Ivana Kholová Fimlab Laboratories, Pathology, Tampere University Hospital, Tampere, Finland Linda Klotz University College of London, Institute of Child Health, Molecular Medicine Unit, London, UK Karl B. Lemström Transplantation Laboratory and Department of Cardiothoracic Surgery, University of Helsinki and Helsinki University General Hospital, Helsinki, Finland ix

x Contributors P. Charles Lin Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD, USA Shin Lin Stanford University School of Medicine, Falk Cardiovascular Research Center, Stanford, CA, USA Marios Loukas Department of Anatomical Sciences, St. George s University School of Medicine, St. George, Grenada Jörg Männer Department of Anatomy and Embryology, University Medicine Göttingen, Göttingen, Germany Antti I. Nykänen Transplantation Laboratory and Department of Cardiothoracic Surgery, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland Jae-Hyeong Park Department of Internal Medicine, Chungnam National University Hospital, Regional Cardiovascular Center, Daejeon, Korea Xianghu Qu Department of Pediatric (Cardiology), Vanderbilt University Medical Center, Nashville, TN, USA Paul Riley Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK Stanley G. Rockson Stanford University School of Medicine, Falk Cardiovascular Research Center, Stanford, CA, USA Sameer Shah Department of Anatomical Sciences, St. George s University School of Medicine, St. George, Grenada R. Shane Tubbs Department of Pediatric Surgery, Children s Hospital, Birmingham, AL, USA Jörg Wilting Department of Anatomy and Cell Biology, University Medicine Göttingen, Göttingen, Germany Wilson Wong MRC Center for Transplantation, King s College London School of Medicine at Guy s, King s and St. Thomas Hospitals, London, UK Todd R. Wuest Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD, USA Seppo Ylä-Herttuala Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland