Cardiac and Vascular Receptors and Signal Transduction
Cellular physiological functions are regulated via signaling mechanisms in essentially any cell type of any organ within the human body. While myocardial cells are unique in that they are interconnected to each other via gap junctions and thus act as an e
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Daniel C. Sigg and Ayala Hezi-Yamit
Abstract
Cellular physiological functions are regulated via signaling mechanisms in essentially any cell type of any organ within the human body. While myocardial cells are unique in that they are interconnected to each other via gap junctions and thus act as an electrical syncytium, a vast number of important cellular receptors and signal transduction pathways allow individual cells to receive and respond to various signals. These receptors and signal transduction pathways play important roles in normal cell/organ functions (their physiology), as well as in disease processes (pathophysiology). It is the aim of this chapter to review the major role and signaling mechanisms of selected physiologically and pathophysiologically important cardiac and vascular receptors, with emphasis on G protein-coupled receptors (e.g., betaadrenergic receptors) and non-G protein-coupled receptor systems, such as guanylyl cyclaserelated receptors (e.g., receptors for nitric oxide). Finally, we will discuss the importance and complexity of inflammation in the pathobiology of coronary artery disease and its treatment. Inflammation plays a very important role in cardiovascular disease. For example, devicebased interventions such as coronary stenting may activate inflammation via a series of complex signaling processes. Importantly, inflammation pathways also play a central role in the elicitation of atherosclerosis, myocardial infarction, and/or heart failure. Keywords
Coupling • G protein receptor • Beta-adrenergic receptor • Alpha-adrenergic receptor • Muscarinic receptor • Receptor cross talk
Abbreviations AC ATP β-AR
Adenylyl cyclase Adenosine triphosphate Beta-adrenergic receptor
D.C. Sigg, MD, PhD (*) FocusStart LLC, 213 4th St. E., Suite 413, St. Paul, MN 55101, USA e-mail: [email protected] A. Hezi-Yamit, PhD Avinger, Inc., 400 Chesapeake Drive, Redwood City, CA 94063, USA
β-ARK cAMP CDK cGMP DES ERK GC GDP GTP IRAK ISR JNK MAPK MCP
Beta-adrenergic receptor kinase Cyclic adenosine monophosphate Cyclin-dependent kinase Cyclic guanosine monophosphate Drug-eluting stent Extracellular signal-regulated kinase Guanylyl cyclase Guanosine diphosphate Guanosine triphosphate Interleukin-1 receptor-associated kinase In-stent restenosis JUN N-terminal kinase Mitogen-activated protein kinase Monocyte chemoattractant protein
© Springer International Publishing Switzerland 2015 P.A. Iaizzo (ed.), Handbook of Cardiac Anatomy, Physiology, and Devices, DOI 10.1007/978-3-319-19464-6_15
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M-CSF NO NOS pRB PTCA SMC TIR TLR TNF TNFR TRAF
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D.C. Sigg and A. Hezi-Yamit
Macrophage colony-stimulating factor Nitric oxide Nitric oxide synthase Retinoblastoma gene product Percutaneous transluminal coronary angioplasty Smooth muscle cell Toll/interleukin-1 receptor Toll-like receptor Tumor necrosis factor Tumor necrosis factor receptor TNFR-associated factor
Introduction
Cellular physiological functions are regulated via signaling mechanisms in essentially any cell type of any organ. While myoc
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