Aberrant vascular smooth muscle cell (VSMC) proliferative responses contribute to the development of neointimal lesions. Cyclic adenosine monophosphate (cAMP) is believed to inhibit VSMC proliferation, and vascular diseases are associated with impairments in cAMP-induced signalling responses involving protein kinase A (PKA) signaling. An enhanced expression of the early growth response protein-1 (Egr-1), a zinc finger transcription factor, has been reported in models of vascular diseases and, a crucial role of Egr-1 in regulating the expression of genes implicated in neointimal formation leading to atherogenesis has been suggested. Various vasoactive factors have been shown to modulate Egr-1 expression in VSMC via mechanisms which remain to be completely understood. Angiotensin-II (Ang-II) is one of the key vasoactive peptides implicated in the pathogenesis of vascular diseases. Ang-II elevates intracellular calcium (Ca2+) through activation of voltage-gated calcium channels as well as store-operated calcium channels. The store-operated calcium entry (SOCE) involves an inositol-3-phosphate receptor (IP3R)-coupled depletion of endoplasmic reticular Ca2+ and a subsequent activation of the stromal interaction molecule 1 (STIM-1) /Orai-1 complex. Although Egr-1 has been demonstrated to be upregulated in a Ca2+-dependent fashion in response to several stimuli, the involvement of STIM-1/Orai-1-dependent signaling in Egr-1 expression in VSMC has never been addressed. Besides, whether Ang-II-induced signaling leading to Egr-1 expression is modulated by cAMP-dependent signaling pathway remains unexplored. Therefore, in the present studies, we have examined the role of Ca2+ signaling in Ang-II-induced Egr-1 expression in VSMC and investigated the contribution of STIM-1 or Orai-1. Additionnaly, we have examined the effect of cAMP on Ang-II-induced expression of Egr-1 and have investigated the associated signalling pathways. Pharmacological blockade of IP3R and SOCE by 2-aminoethoxydiphenylborate (2-APB) decreased Ang-II-induced Ca2+ release and attenuated Ang-II-induced enhanced expression of Egr-1 protein and mRNA levels. Egr-1 upregulation was also suppressed following blockade of calmodulin and CaMKII. Furthermore, RNA interference-mediated depletion of STIM-1 or Orai-1 attenuated Ang-II-induced Egr-1 expression, as well as Ang-II-induced phosphorylation of ERK1/2 and CREB. Moreover, isoproterenol (ISO) and forskolin (FSK), two respective receptor and non-receptor activators of adenylate cyclase, attenuated Ang-II-induced Egr-1 expression in a dose-dependent fashion. Similar responses were observed using non-specific (dibutyryl-cAMP) and PKA-specific (Benzoyl-cAMP) analogs of cAMP, as well as a broad spectrum inhibitor of intracellular phosphodiesterase activity (isobutylmethylxanthine). The inhibition of Ang-II-induced Egr-1 expression was accompanied by an increase in serine 157 phosphorylation of the vasodilator-activated phosphoprotein (VASP), a marker of PKA activity, and this was associated with a concomitant decrease in ERK phosphorylation. Pharmacological blockade of PKA using H89 decreased VASP phosphorylation, restored Ang-II-induced ERK phosphorylation and abolished ISO- and FSK-mediated inhibition of Ang-II-induced Egr-1 expression. In summary, our data demonstrate that STIM-1/Orai-1/Ca2+-dependent signaling pathways mediate Ang-II-induced Egr-1 expression in A-10 VSMC and suggest that PKA-mediated suppression of Ang-II-induced Egr-1 expression and phosphorylation of ERK may be among the mechanisms by which cAMP exerts its vasoprotective effects. In addition, our data supports the notion that stimuli-induced regulation of Egr-1 expression involves the participation of signaling cascades downstream of ERK in VSMC.

The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References

This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.

Epigenetic Regulation in the Nervous System addresses current understanding of the roles of epigenetic processes at the molecular/cellular level, their impact on neural development and behavior, and the potential roles of these mechanisms in neurological and psychiatric disorders. This award-winning volume spans molecular epigenetics, development, cellular physiology and biochemistry, synaptic and neural plasticity, and behavioral models, and is unique in covering epigenetically based disorders of the central nervous system.Behavioral epigenetics is the study of how environmental factors alter behavior, addressing the fundamental mechanisms that shape development and individual vulnerability/resilience to adverse behavioral outcomes. By understanding the molecular mechanisms involved in epigenetic modulation, researchers may be able to develop targeted therapies for those individuals in whom it malfunctions.Edited by the most highly regarded leaders in the field, this book offers a comprehensive review of behavioral epigenetics and a balanced treatment of the strengths and weaknesses in experimentation in this area. Covering background material as well as topics of current interest, it serves both as a cutting-edge resource and a foundational reference. The book will benefit neuroscience researchers and graduate students with an interest in the links between gene regulation and behavior, as will clinicians dealing with disorders such as addiction, depression, and schizophrenia. - BMA Medical Book Awards 2014 - Highly Commended, Neurology, British Medical Association - BMA Medical Book Awards 2014 - First Prize, Neurology, British Medical Association - 2013 PROSE Award winner for Best in Reference Works and Best Single Volume Reference in Science from the Association of American Publishers - Presents a unified view of epigenetic mechanisms from behavior to genes and everything in between - Discusses clinically relevant disorders in the context of epigenetics research, making the volume appealing to clinicians as well as basic scientists - Provides numerous practical examples for the new investigator to facilitate implementation of research in neuroepigenetics

In the last several years, the development of reagents that recognize smooth muscle-specific proteins has enabled researchers to identify smooth muscle cells (SMC) in tissue undergoing both differentiation and repair. These developments have led to increased research on SMC. The latest volume in the Biology of the Extracellular Matrix Series takes a current and all-encompassing look at this growing area of research. Devoted entirely to the subject of SMC, the book covers a diversity of topics-from SMC architecture and contractility to differentiation and gene expression in development. It also examines the proliferation and replication of SMC and its role in pharmacology and vascular disease. A must for cell, developmental, and molecular biologists, this book also will appeal to cardiologists, pathologists, and biomedical researchers interested in smooth muscle cells. - Presents a molecular, genetic, and developmental perspective of the vas smooth muscle cell - Overview sections highlight key points of chapters, including the clinical relevance of the research and expectations for future study - Appeals to both the basic biologist and to the biomedical researcher of vascular disease

This volume contains 17 short review articles classified into 3 parts. Part I consists of 7 articles dealing with basic aspects of contractile mechanism in skeletal and smooth muscle cells and also function of melanocytes having many properties common to those of smooth muscles. Part II and Part III contain articles dealing with pathological aspects of cardiac and smooth muscle cell functions, and dealing with factors influencing structure and function of cardiac and smooth muscle cells and tissues. The Editor believes that these articles are stimulating and informative for readers interested in basic, pathological and clinical aspects of muscle cells and tissues.

New updated edition first published with Cambridge University Press. This new edition includes 29 chapters on topics as diverse as pathophysiology of atherosclerosis, vascular haemodynamics, haemostasis, thrombophilia and post-amputation pain syndromes.