Pathophysiology of Pulmonary Hypertension

Pathophysiology of Pulmonary Hypertension

Yuansheng Gao, J. Usha Raj
ISBN: 9781615047604 | PDF ISBN: 9781615047611
Hardcover ISBN:9781615047680
Copyright © 2018 | 118 Pages | Publication Date: November, 2017

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Pulmonary hypertension is a life-threatening disease with no known cure. Here we provide a concise yet comprehensive review of the current knowledge about the pathophysiology of pulmonary hypertension (PH). The underlying signaling mechanisms involved in pulmonary vascular remodeling and the exaggerated vascular contractility, two characteristic features of pulmonary hypertension, are discussed in depth. The roles of inflammation, immunity, and right ventricular function in the pathobiology of pulmonary hypertension are discussed. The epidemiology of the five groups of pulmonary hypertension (World Health Organization classification; Nice, 2013) is also briefly described. A clear understanding of our current knowledge about the pathogenesis of PH is essential for further exploration of the underlying mechanisms involved in this disease and for the development of new therapeutic modalities. This book should be of interest to researchers and graduate students, both in basic research and in clinical settings, in the fields of pulmonary vascular biology and pulmonary hypertension.

Table of Contents

1. Introduction
2. Classification of Pulmonary Hypertension
3. Epidemiology of Pulmonary Hypertension
4. Pathophysiology of Pulmonary Hypertension
5. Mechanisms of Vascular Remodeling in PH
6. Mechanisms of Excessive Pulmonary Vasoconstriction in PH
Concluding Remarks
References
Author Biographies

About the Author(s)

Yuansheng Gao, Peking University Health Science Center
Yuansheng Gao, Ph.D., received his Ph.D. in Physiology (1990; advisor: Paul M. Vanhoutte) from Mayo Graduate School, Rochester, Minnesota and postdoctoral training in Professor Vanhoutte's laboratory at the Baylor College of Medicine, Houston, Texas (1990-1992). He worked in Professor J. Usha Raj's laboratory from 1992 to 2002 as an Adjunct Assistant/Associate Professor at Harbor-UCLA Medical Center, Los Angeles, California. Since 2002 he serves as Professor of Pathophysiology in Peking University Health Science Center, Beijing, China. He has been an Honorary Professor of Department of Pharmacology and Pharmacy in the University of Hong Kong, China since 2014. He has served as the council member of Asian Society for Vascular Biology since 2005 and the review editor for the journal Frontiers in Vascular Physiology since 2011. He has worked on the signaling transduction of pulmonary and coronary vasculature for nearly 30 years and has published over 90 original research and review articles in this field.

J. Usha Raj, University of Illinois, College of Medicine at Chicago
J. Usha Raj, M.D., is the Anjuli S. Nayak Professor of Pediatrics, University of Illinois, Chicago, Illinois. She was the Head of Pediatrics at UIC from 2008 to 2015 and Chief of Neonatology at Harbor-UCLA from 1995 to 2008. Dr. Raj is nationally and internationally known as a clinician-scientist for her research on the mechanisms involved in the development of pulmonary hypertension. Her work has been funded by the National Institutes of Health (NIH) for over 32 years. She is a co-investigator on grants funded by the NIH and Center for Medicare and Medicaid that are designed to improve care for the underserved pediatric population in Chicago. She has published over 165 peer-reviewed scientific manuscripts in high-quality journals. She has received numerous awards from International Scientific Societies, including the Scientific Recognition and Distinguished Achievement Awards from the American Thoracic Society and the Julius Comroe Jr. Distinguished Lectureship and election as a fellow to the society by the American Physiological Society. She received an honorary doctorate (honoris causa) from the University of Lausanne in June 2016 in recognition of her many contributions in research and mentorship. She is a member of the World Task Force on Pediatric Pulmonary Hypertension and an advisor to the Pediatric Pulmonary Hypertension network in North America. She has been selected for the "U.S. News & World Report" Top Doctors list.

Reviews

This is a most instructive, delightful little book. First, the authors refresh the readers' understanding of the major health problem represented by pulmonary hypertension, emphasizing the important differences between the pulmonary and systemic circulation. They then clearly define the different forms of this syndrome, as accepted by the medical community in general and the WHO in particular, and summarize its epidemiology in a clear and rational way, subdividing the occurrence in function of unknown [idiopathic forms], known [caused by heart disease, pulmonary disorders or repeated thromboembolic events] or less defined multifactorial [hematologic, systemic or metabolic disorders] causes, with a focus on the often ignored occurrence in children. They then discuss the pathophysiology with the underlying remodeling of the pulmonary vascular wall, identifying major culprits: impaired protection by prostacyclin and nitric oxide and/or aberrant production of endothelin-1, apparently responsible for most idiopathic forms of pulmonary arterial hypertension. But they also stress how the syndrome can follow abnormal cardiac function (because of pressure overload in the pulmonary blood vessels) or chronic exposure to hypoxia [with the prominent role played by hypoxia-inducible (HIFs) and growth (VEGF)], insisting on the role of immune and inflammatory responses, not to mention their description of repeated pulmonary embolism. They masterfully describe the impact of the heightened pulmonary pressure on the right ventricle. Their chapter on mechanisms leading to vascular remodeling during pulmonary hypertension is a classical piece of rational scientific writing, elaborating in turn on altered ion channel activity (a most complex affair that they unravel clearly), perturbed interactions between endothelial and vascular smooth muscle cells (bringing nitric oxide and endothelin-1 back in the picture but not forgetting a long-time villain, serotonin), aberrant growth factor signaling and the facilitator role of hypoxia, the for most readers unknown contribution of extracellular vesicles, the emerging modulation by microRNAs, the importance of genetic and epigenetic modifications, as well as the potential contribution of signals from the adventitia (also a newcomer in vascular pathophysiology). The authors then move on to discuss in more details the causes underlying the excessive vasoconstrictor responses that accompany (cause?) pulmonary hypertension, discussing the failure of the nitric oxide pathway, the reduction in prostacyclin-production, the exaggerated production of endothelin-1 and the resulting activation of Rho-kinase signaling, the obvious deleterious role of reactive oxygen species, and the often unsuspected role of metabolic disturbances. The different chapters of this book not only will help the reader to appreciate the complexity of the multiple mechanisms that can lead to pulmonary hypertension, but also to understand much better the basis for the current therapeutic interventions. Although the authors undertake to address the cellular molecular mechanisms that underlie the occurrence of pulmonary hypertension, they do so with great clarity, with a wealth of most instructive and clear schematics, basing their writings on a thesaurus of references. This book is a must for anyone, whether basic scientist, clinical researcher or clinician interested in the major health problem represented by pulmonary hypertension. It also sets the stage for further exploration of the physiopathology and hence for the appropriate treatment of the syndrome.
Paul M. Vanhoutte MD, PhD

Reviews (1)
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