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This chapter addresses the role of neurotrophins in the development of the heart, blood vessels, and neural circuits that control cardiovascular function, as well as the role of neurotrophins in the mature cardiovascular system. The cardiovascular system includes the heart and vasculature whose functions are tightly controlled by the nervous system. Neurons, cardiomyocytes, endothelial cells, vascular smooth muscle cells, and pericytes are all targets for neurotrophin action during development. Neurotrophin expression continues throughout life, and several common pathologies that impact cardiovascular function involve changes in the expression or activity of neurotrophins. These include atherosclerosis, hypertension, diabetes, acute myocardial infarction, and heart failure. In many of these conditions, altered expression of neurotrophins and/or neurotrophin receptors has direct effects on vascular endothelial and smooth muscle cells in addition to effects on nerves that modulate vascular resistance and cardiac function. This chapter summarizes the effects of neurotrophins in cardiovascular physiology and pathophysiology. [ABSTRACT FROM AUTHOR]

Signaling pathways mediated by receptor tyrosine kinases (RTKs) are among the most important pathways regulating various functions and behaviors in mammalian cells. Although many studies performed over several decades have revealed the molecular mechanisms underlying the cellular events regulated by these pathways, the overall structures of the pathways remain unclear, especially their quantitative properties. A technology has emerged that can potentially address these issues. Recent developments in optical microscopy and molecular biology allow us to visualize the behaviors of single RTK molecules and their association partners with fluorescent probes in living cells. Using the quantitative nature of these single-molecule measurements, we studied the signaling of epidermal growth factor (EGF) and nerve growth factor (NGF), both of which stimulate RTK systems. Single-molecule analyses revealed molecular dynamics and kinetics that cannot be demonstrated with conventional biochemical methods. These include the kinetic transitions of these receptors induced by ligand binding, signal amplification by the dynamic interactions between active and inactive receptors, downstream signaling with a memory effect exerted by the receptor molecule, and shifts in the motional modes of ligand-receptor complexes. These novel insights obtained from single-molecule studies suggest that detailed models of RTK signaling, which involve signal processing depend on protein dynamics. [ABSTRACT FROM AUTHOR]