Modern mechanobiology converges both engineering and medicine to address personalized medicine. This book is built on the previously well-received edition, Hemodynamics and Mechanobiology of Endothelium. The central theme is "omic" approaches to mechanosignal transduction underlying tissue development, injury, and repair. A cadre of investigators has contributed to the chapters, enriching the interface between mechanobiology and precision medicine for personalized diagnosis and intervention. The book begins with the fundamental basis of vascular disease in response to hemodynamic shear stress and then details cardiovascular development and regeneration, valvular and cardiac morphogenesis, mechanosensitive microRNA and histone unfolding, computational fluid dynamics, and light-sheet imaging. This edition represents a paradigm shift from traditional biomechanics and signal transduction to transgenic models, including novel zebrafish and chick embryos, and targets a wider readership from academia to industry and government agencies in the field of mechanobiology.
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Yes, you can access Modern Mechanobiology by Juhyun Lee, Sharon Gerecht, Hanjoong Jo, Tzung Hsiai, Juhyun Lee, Sharon Gerecht, Hanjoong Jo, Tzung Hsiai in PDF and/or ePUB format, as well as other popular books in Medicine & Biotechnology in Medicine. We have over one million books available in our catalogue for you to explore.
Suowen Xu and Zheng Gen Jin Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Avenue, Rochester, NY, 14623, USA [email protected]; [email protected]
Endothelial cells line the innermost layer of a blood vessel and regulate multiple functional aspects of vascular homeostasis, such as vascular tone, inflammation, vessel permeability, and angiogenesis. Endothelial cells possess multiple specialized mechanosensing molecules or microstructures (termed āmechanosensorsā) that sense different patterns of blood flow (in a concerted manner). Mechanosensing is a prerequisite step for integrating the mechanosignal into endothelial cells and leads to different patterns of endothelial gene expression. Emerging evidence using genetically engineered mice and pharmacological modulators has shown that these mechanosensors are critical regulators of endothelial function and probably the pathogenesis of atherosclerosis-related cardiovascular diseases. In this chapter, we delineate the specific role of each identified mechanosensor in vascular endothelial cell biology and atherosclerosis and highlight the possibility of targeting these mechanosensors to treat atherosclerosis.
1.1 Introduction
Cardiovascular diseases caused by atherosclerosis represent the main cause of global morbidity and mortality [1, 2]. Atherosclerosis is a chronic inflammatory disease [3] and a focal disease in which atherosclerotic plaques preferentially developed in regions of disturbed/turbulent flow (such as arterial branching points, bifurcations, and inner curvature) but less in regions of laminar flow (such as thoracic aorta) [4ā8]. Therefore, the development of atherosclerosis itself is heterogeneous, and this focal nature of atherosclerosis makes the study of different patterns of hemodynamic forces an effective therapeutic strategy to combat atherosclerosis.
Endothelial cells (ECs) are one major type of vascular cells. They line the intima by forming an endothelial monolayer, thereby separating circulating blood from human body [9]. In addition to being a natural barrier between blood components and vessel wall, they are the specific cell type that are in direct contact with blood flow and vessel wall. On the endothelial surface, there are many sensing molecules or microdomains that can serve as effective mechanosensors. They sense and transduce the mechanosignal exerted by shear stress to the inside of ECs. Dysfunctionality of these sensors leads to the alteration of endothelial pathways, gene expression, and endothelial functions, such as vascular tone, vessel stability, and leukocyte adhesion (Fig. 1.1). In this chapter, we provide a systematic overview of the up-to-date functions and mechanisms of different mechanosensors in mediating endothelial function and atherosclerosis. We also highlight future direction in mechanosensor-based studies, without an aim to accelerate cardiovascular drug discovery.
1.2 Shear Stress and Endothelial Phenotype
Generally, there are two major types of shear stress: one is the laminar flow and the other is disturbed flow. The different flow patterns were generated by different hemodynamic forces using different shear stress systems, such as plate viscometer, flow chamber, ibidi system, and other microfluidic systems. Mounting evidence in the past has shown that laminar flow protects against endothelial dysfunction and atherosclerosis, by promoting an endothelial protective and atheroprotective transcriptional program, mediated by transcriptional factors, such as KrĆ¼ppel-like factor-2 (KLF2) [10ā12], KLF4 [13ā15], and Nrf21 [16]. In contrast, disturbed flow promotes endothelial dysfunction and atherosclerosis via atherogenic transcriptional factors, such as nuclear factor kappa light chain enhancer of activated B cells (NF-icB) [17], yes-associated protein (YAP) [18ā20], and HIF12 [21, 22] (Fig. 1.2). Many drugs, such as statins [23, 24], resveratrol [24ā26], tannic acids [27], and histone deacetylase inhibitor SAHA3 [28], mimic laminar flow response by upregulating KLF2 expression and activity. On the other hand, many proatherogenic factors, such as lipopolysaccharide (LPS) [29] and tumor necrosis factor-alpha (TNF-Ī±) [30], mimic the disturbed flowā induced response by activating NF-x:B and downregulating KLF2 expression, suggesting the possibility of target mechanosensitive transcriptional factors modulating atherosclerosis.
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1 Nuclear factor erythroid 2ārelated factor 2.
2 Hypoxia-inducible factor-1.
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3 Suberoyl+anili...
Table of contents
Cover
Half Title
Title Page
Copyright Page
Table of Contents
Preface
1. Shear Stress, Mechanosensors, and Atherosclerosis
2. Role of KrĆ¼ppel-Like Factors in Endothelial Cell Function and Shear StressāMediated Vasoprotection
3. Aortic Valve Endothelium Mechanobiology
4. Mechanotransduction of Cardiovascular Development and Regeneration
5. Mechanotransduction in Heart Formation
6. Mechanotransduction in Cardiovascular Development and Regeneration: A Genetic Zebrafish Model
7. Mechanosensitive MicroRNAs in Health and Disease
8. Biomechanics in Cardiac Development Using 4D Light-Sheet Imaging