New Insights Into Cardiovascular Mechanobiology Molecular Basis And Clinical Perspectives

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 will cover the cutting-edge developments in molecular and cellular mechanobiology to date. Readers will have a clear understanding of mechanobiology at the molecular and cellular levels, encompassing the mechanosensors, transducers, and transcription. An integrative approach across different scales from molecular sensing to mechanotransduction and gene modulation for physiological regulation of cellular functions will be explored, as well as applications to pathophysiological states in disease. A comprehensive understanding of the roles of physicochemical microenvironment and intracellular responses in determining cellular function in health and disease will also be discussed.

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 Research Topic is Volume II of a series. The previous volume, which has attracted over 40,000 views can be found here: Bioengineering and Biotechnology Approaches in Cardiovascular Regenerative MedicineCardiovascular diseases continue to be the leading cause of death while available clinical interventions have limited contributions to heart repair and regeneration. Cardiovascular regenerative medicine, characterized by a unique integration of biology, physical sciences, and bioengineering principles, has emerged as one of the most promising fields of translational research to regenerate the adult human heart.

Mechanobiology-the study of the effects of mechanical environments on the biological processes of cells-has evolved from traditional biomechanics via the incorporation of strong elements of molecular and cell biology. Currently, a broad range of organ systems are being studied by surgeons, physicians, basic scientists, and engineers. These mechanob