Cardiovascular Mechanobiology 2nd Edition

Biomechanical forces play a major role in organ development, shape and function. When exceeding the physiological range, however, they may become detrimental for organ structure and function. This is probably best exemplified by the cardiovascular system, with both the heart and blood vessels being continuously exposed to the biomechanical forces exerted by the flow of blood. In the heart, it is the build-up of pressure inside the ventricles that allows the ejection of blood into the pulmonary and systemic circulation. The luminal diameter of the small arteries in both parts of the circulation determines the resistance to flow. Hence it also determines the level of blood pressure in both the pulmonary and systemic circulation and thus the afterload for both ventricles of the heart. A narrowing of the small arteries (e.g. due to an increase in tone) therefore leads to an increase in blood pressure in the affected part of the circulation. This will decrease organ perfusion but increase the afterload for the corresponding ventricle of the heart. Consequently, the affected ventricle must build up more pressure to maintain cardiac output. However, if the rise in blood pressure (pulmonary or arterial hypertension) persists the increase in wall tension can no longer be compensated by active constriction, thereby forcing the ventricle to resort to other means to unload itself. Typically, this is achieved by structural alterations in its wall which becomes thicker (hypertrophy) and stiffer (remodelling of the extracellular matrix). Ultimately, this maladaptive response may lead to dysfunction and eventually failure of the ventricle, which would only be able to eject a significantly smaller amount of blood into circulation. The increase in wall tension has resulted in an increased stretching of the cardiomyocytes as well as non-cardiomyocytes, such as cardiac fibroblasts, which in turn alters both their phenotype and their environment. Research into the mechanobiology of the heart aims to unravel the molecular and cellular mechanisms underlying the physiological response of the heart to load to learn what goes wrong when the heart is faced with sustained pressure overload. This may pave the way to therapeutically interfering with this maladaptive response and thus preventing either the initial hypertrophy or its transition into heart failure. While the heart is mainly subjected to pressure hence stretch as a biomechanical force, the mechanobiology of vascular cells is somewhat more complex. Endothelial cells lining the luminal surface of each blood vessel are continuously subjected to the viscous drag of flowing blood (referred to as fluid shear stress). Fluid shear stress mainly affects the endothelial cells of the small arteries and arterioles, maintaining them in a dormant phenotype. If blood flow is disturbed (e.g. at arterial bifurcations or curvatures) fluid shear stress declines and may give rise to a shift in phenotype of the endothelial cells. A shift from anti-inflammatory to pro-inflammatory in combination with the reduced flow at these sites may enable leukocyte recruitment and diapedesis, which results in a pro-inflammatory response in the vessel wall. Endothelial cells and in particular vascular smooth muscle cells are subjected to another biomechanical force: the blood pressure. Volume-dependent distention of the vessel wall (which can be achieved through an increase in blood flow) results in an increase in wall tension, thereby stretching of the endothelial and smooth muscle cells. Like the cardiomyocytes of the heart, the vascular smooth muscle cells of the small arteries and arterioles try to normalise wall tension by active constriction, which cannot be maintained for long. These cells subsequently undergo hypertrophy or hyperplasia (depending on the size of the blood vessel) and remodel the extracellular matrix so that the vessel wall also becomes thicker and stiffer. This in turn raises their resistance to flow and may contribute to the increase in blood pressure in either the pulmonary or systemic circulation. Research into the mechanobiology of the blood vessels aims to unravel the molecular and cellular mechanisms underlying the physiological response of the vascular cells to pressure (wall tension) and flow (shear stress). It also aims to uncover what goes wrong (e.g. in arteriosclerosis or hypertension) and to eventually specifically interfere with these maladaptive remodelling processes. The aforementioned aspects of cardiovascular mechanobiology along with many more facets of this fascinating, timely and highly clinically relevant field of research are addressed by the original research and review articles within this Research Topic.

This volume of the series Cardiac and Vascular Biology presents the most relevant aspects of vascular mechanobiology along with many more facets of this fascinating, timely and clinically highly relevant field. Mechanotransduction, mechanosensing, fluid shear stress, hameodynamics and cell fate, are just a few topics to name. All important aspects of vascular mechanobiology in health and disease are reviewed by some of the top experts in the field. This volume, together with a second title on cardiac mechanobiology featured in this series, will be of high relevance to scientists and clinical researchers in the area of vascular biology, cardiology and biomedical engineering.

This book presents the latest findings in the field of cardiac mechanobiology in health and disease. Cardiac mechanobiology provides knowledge of all aspects of mechanobiology of the heart. Cardiomyogenesis is discussed as well as the mechanobiology of cardiac remodeling and regeneration. The molecular mechanisms of mechanoperception and mechanotransduction in cardiomyocytes are explained, as well as stretch induced differentiation of cardiomyocytes derived from induced pluripotent stem cells. This volume of the series Cardiac and Vascular Biology complements the volume Vascular Mechanobiology in Physiology and Disease (volume 8) published in this series. The book is aimed at clinicians as well as researchers in cardiovascular biology, bioengineering and biophysics, and also represents an educational resource for young researchers and students in these fields.

Mechanobiology—the study of the effects of mechanics on biological events—has evolved to answer numerous research questions. Mechanobiology Handbook 2nd Edition is a reference book for engineers, scientists, and clinicians who are interested in mechanobiology and a textbook for senior undergraduate to graduate level students of this growing field. Readers will gain a comprehensive review of recent research findings as well as elementary chapters on solid mechanics, fluid mechanics, and molecular analysis techniques. The new edition presents, in addition to the chapters of the first edition, homework problem sets that are available online and reviews of research in uncovered areas. Moreover, the new edition includes chapters on statistical analysis, design of experiments and optical imaging. The editors of this book are researchers and educators in mechanobiology. They realized a need for a single volume to assist course instructors as a guide for didactic teaching of mechanobiology to a diverse student body. A mechanobiology course is frequently made up of both undergraduate and graduate students pursuing degrees in engineering, biology, or integrated engineering and biology. Their goal was to present both the elementary and cutting-edge aspects of mechanobiology in a manner that is accessible to students from many different academic levels and from various disciplinary backgrounds. Moreover, it is their hope that the readers of Mechanobiology Handbook 2nd Edition will find study questions at the end of each chapter useful for long-term learning and further discussion. Comprehensive collection of reviews of recent research Introductory materials in mechanics, biology, and statistics Discussion of pioneering and emerging mechanobiology concepts Presentation of cutting-edge mechanobiology research findings across various fields and organ systems End of chapter study questions, available online Considering the complexity of the mechanics and the biology of the human body, most of the world of mechanobiology remains to be studied. Since the field is still developing, the Mechanobiology Handbook raises many different viewpoints and approaches with the intention of stimulating further research endeavours.

Mechanobiology: From Molecular Sensing to Disease will provide a review of the current state of understanding of mechanobiology and its role in health and disease. It covers: Current understanding of the main molecular pathways by which cells sense and respond to mechanical stimuli, A review of diseases that with known or purported mechanobiological underpinnings; The role of mechanobiology in tissue engineering and regenerative medicine; Experimental methods to capture mechanobiological phenomena; Computational models in mechanobiology. Presents our current understanding of the main molecular pathways by which cells sense and respond to mechanical stimuli Provides a review of diseases with known or purported mechanobiological underpinnings Includes the role of mechanobiology in tissue engineering and regenerative medicine Covers experimental methods to capture mechanobiological phenomena

This book provides a balanced presentation of the fundamental principles of cardiovascular biomechanics research, as well as its valuable clinical applications. Pursuing an integrated approach at the interface of the life sciences, physics and engineering, it also includes extensive images to explain the concepts discussed. With a focus on explaining the underlying principles, this book examines the physiology and mechanics of circulation, mechanobiology and the biomechanics of different components of the cardiovascular system, in-vivo techniques, in-vitro techniques, and the medical applications of this research. Written for undergraduate and postgraduate students and including sample problems at the end of each chapter, this interdisciplinary text provides an essential introduction to the topic. It is also an ideal reference text for researchers and clinical practitioners, and will benefit a wide range of students and researchers including engineers, physicists, biologists and clinicians who are interested in the area of cardiovascular biomechanics.

The book represents a paradigm shift from the traditional static model of investigation of oxidative biology to the dynamic model of vascular oxidative stress. The investigation of vascular biology and cardiovascular medicine is made possible by the use of tissue engineering, nanotechnology and stem cell research. This is the first textbook to target a wide readership from academia to industry and government agencies in the field of cardiovascular diseases.