Modern Mechanobiology Convergence of Biomechanics, Development, and Genomics

Cover
Half Title
Title Page
Copyright Page
Table of Contents
Preface
Chapter 1: Shear Stress, Mechanosensors, and Atherosclerosis
	1.1: Introduction
	1.2: Shear Stress and Endothelial Phenotype
	1.3: Mechanosensors in Atherosclerosis
		1.3.1: PECAM1/VEGFR2/VE-Cadherin Mechanosensing Complex
		1.3.2: TRPV4
		1.3.3: Piezo1
		1.3.4: Primary Cilia
		1.3.5: Caveolae
		1.3.6: Rap1
		1.3.7: Glycocalyx
		1.3.8: Integrins
		1.3.9: GPCR
		1.3.10: Emerging New Mechanosensors
	1.4: Conclusions and Perspectives
Chapter 2: Role of Krüppel-Like Factors in Endothelial Cell Function and Shear Stress–Mediated Vasoprotection
	2.1: Introduction
	2.2: Krüppel-Like Factors
		2.2.1: Krüppel-Like Factor 2
			2.2.1.1: Regulation of KLF2 by laminar shear stress
			2.2.1.2: Targets of shear stress–induced KLF2
		2.2.2: Krüppel-Like Factor 4
	2.3: Future Directions
Chapter 3: Aortic Valve Endothelium Mechanobiology
	3.1: Introduction
		3.1.1: The Aortic Valve
		3.1.2: Aortic Valve Cell Types
		3.1.3: Calcific Aortic Valve Disease
		3.1.4: Aortic Valve Mechanics
		3.1.5: The Role of Shear Stress in the Aortic Valve Endothelium
	3.2: Shear Stress Waveforms of Aortic Valves
		3.2.1: Aortic Valve Shear Stress Waveforms Are Estimated
		3.2.2: Aortic Valves Have Side-Specific Shear Stress Waveforms
		3.2.3: Bicuspid Aortic Valves Have Abnormal Shear Stress Waveforms
	3.3: Valve Endothelial Response to Shear Stress
		3.3.1: Devices Designed for Studying VEC Response to Shear Stress
		3.3.2: VEC Phenotype Is Shear Stress Regulated
		3.3.3: Side-Dependent Hemodynamics Correlate with Side-Specific Phenotypes
	3.4: Shear Stress-Regulated Mechanisms of Valve Homeostasis and Disease
		3.4.1: Endothelial to Mesenchymal Transformation
		3.4.2: eNOS, Nitric Oxide, Notch1, and Cadherin-11
		3.4.3: Krüppel-Like Factor 2
		3.4.4: Transforming Growth Factor-β
	3.5: Conclusions
Chapter 4: Mechanotransduction of Cardiovascular Development and Regeneration
	4.1: Introduction
	4.2: A Primer on Cardiovascular Anatomy and Physiology
		4.2.1: Cardiovascular Anatomy
		4.2.2: Heart Development
		4.2.3: Vascular Development
	4.3: Mechanics of the Cardiovascular System
		4.3.1: Cardiac Cycle
		4.3.2: Blood Mechanics
		4.3.3: Cardiovascular Extracellular Matrix Composition
	4.4 Engineering Approaches to Studying Mechanotransduction in Cardiovascular Development
		4.4.1: Cell Sources
			4.4.1.1: Pluripotent cells
			4.4.1.2: Mesenchymal-derived stem cells
			4.4.1.3: Progenitor cells
		4.4.2: Extracellular Matrix Regulation of Cardiovascular Development and Regeneration
			4.4.2.1: Decellularized tissue
			4.4.2.2: Natural extracellular matrices
			4.4.2.3: Synthetic matrices
			4.4.2.4: Oxygen tension and mechanotransduction
		4.4.3: BioMEMS
			4.4.3.1: Microfluidic platforms
			4.4.3.2: Micropatterned tools
		4.4.4: 3D Printing Technology
	4.5: Conclusions and Future Directions
Chapter 5: Mechanotransduction in Heart Formation
	5.1: Introduction: Blood Flow Dynamics and Mechanotransduction
		5.1.1: Mechanical Stimuli in the Cardiovascular System
		5.1.2: Sensing Blood Flow
		5.1.3: Responses to Blood Flow
	5.2: Cardiovascular Development
		5.2.1: Heart Formation
		5.2.2: Heart Malformation
	5.3: Effect of Blood Flow on Cardiac Formation
		5.3.1: Animal Models of Cardiac Development
		5.3.2: Early Embryonic Cardiac Remodeling in Response to Altered Hemodynamics
			5.3.2.1: Effects typically associated with altered wall shear stress
			5.3.2.2: Effects typically associated with altered blood pressure
		5.3.3: Cardiac Malformation Phenotypes after Hemodynamic Interventions
	5.4: Conclusions
Chapter 6: Mechanotransduction in Cardiovascular Development and Regeneration: A Genetic Zebrafish Model
	6.1: Introduction of Zebrafish as a Cardiovascular Model
	6.2: ECG in Zebrafish
	6.3: Mechanosensitive Pathways Modulate Vascular Development and Regeneration in Zebrafish
		6.3.1: Notch Signaling in Vascular Regeneration
		6.3.2: PKCε/PFKFB3 Pathway in Vascular Regeneration
		6.3.3: The Wnt/Ang-2 Pathway in Vascular Development and Regeneration
	6.4: Hemodynamic Fluid Force Promotes Cardiac Development via Mechanosensitive Notch Signaling in Zebrafish
	6.5: Future Perspective
		6.5.1: The Regulation of Metabolic Pathways by Mechanical Forces
		6.5.2: Interaction and Synergy of Mechanosensitive Pathways
		6.5.3: Mechanotransduction of Different Mechanical Forces in Cardiac Morphogenesis
	6.6: Conclusion and Summary
Chapter 7: Mechanosensitive MicroRNAs in Health and Disease
	7.1: Introduction
	7.2: MicroRNA in Hemodynamics Sensing
	7.3: MicroRNA in Extracellular Matrix Regulation
	7.4: MicroRNA in Stretch Sensing
	7.5: MicroRNA in Additional Diseases
	7.6: Targeting Dysregulated Mechanosensitive MicroRNAs in Diseases
Chapter 8: Biomechanics in Cardiac Development Using 4D Light-Sheet Imaging
	8.1: Introduction
		8.1.1: Hemodynamic Shear Stress
		8.1.2: Cardiac Trabeculation
		8.1.3: Zebrafish as a Model Animal
	8.2: Light-Sheet Technology
		8.2.1: Introduction of Light-Sheet Imaging
		8.2.2: Application of Traditional Light-Sheet Imaging
		8.2.3: 4D Methods to Image in vivo Zebrafish Cardiac Mechanics and Trabeculation
	8.3: Quantification of Hemodynamic Shear Stress
		8.3.1: Introduction of CFD
		8.3.2: Combination of Light-Sheet Imaging and CFD
		8.3.3: Application of Zebrafish Cardiac Mechanics and Trabeculation: Morphology
	8.4: Mechanobiology of Zebrafish Trabeculation
		8.4.1: Introduction to Notch Signaling
		8.4.2: Mechanotransduction of Notch, Including in vitro Cell Studies
		8.4.3: Applications of Different Types of Shear Stress for Ventricular Morphology
		8.4.4: Notch Signaling for Trabeculation
		8.4.5: Link Hemodynamic Shear Stress and Trabeculation: Pattern of Trabeculae
Index