Endothelial dysfunction, cytokines and their genetic variations.
Endothelium: molecular aspects of metabolic disorders. Engin AB, Engin A, eds. Boca Raton, FL: CRC Press, 2013 Jun; :151-170
The endothelium is a major regulator of vascular homeostasis. Alterations in endothelial cell function such as impaired vasodilatory responses, increased prothrombotic/procoagulant activity and proinflammatory/prothrombotic states have been linked to a number of cardiovascular and metabolic disorders. Chronic inflammation is widely accepted as a common pathophysiological mechanism leading to endothelial dysfunction (Stenvinkel 2001, Szmitko et al. 2003, Csiszar et al. 2008, Rabelink et al. 2010). A body of evidence has shown that persistent inflammation can promote a pro-atherogenic environment in the vessel wall (Vercellotti 2001, Corrado and. Novo 2005, Lamon and Hajjar 2008). Under inflammatory activation, endothelial cells can express a number of inflammatory cytokines, including, but not limited to, interleukin-1 (IL-1), interleukin-6, (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNFalpha) and MCP-1 (monocyte chemotactic protein-1). This increases the expression of adhesion molecules such as intercellular adhesion molecules (ICAMs), vascular cell adhesion molecule-1 (VCAM-1), P-selectins, E-selectins, and chemokines by vascular endothelial cells. Upregulation of adhesion molecules, chemokines and production of fibrinogen and tissue plasminogen activator inhibitors participate in the inflammatory response and contribute to a prothrombotic state. The balance between pro- and anti-inflammatory cytokines regulates the inflammatory response and thrombus formation. Endothelial dysfunction has been proposed as an early event in the atherosclerotic process and provides an important link between diseases such as hypertension, coronary artery disease, diabetes, and chronic heart and renal failure (Kinlay and Ganz 1997, Puddu et al. 2000, Bolton et al. 2001, Fischer et al. 2005, Bakker et al. 2009). This chapter summarizes current knowledge regarding the involvement of cytokines and their genetic variations in endothelial dysfunction related diseases.
Metabolic-disorders; Molecular-biology; Molecular-structure; Cell-alteration; Cell-biology; Cell-function; Cell-metabolism; Cellular-function; Cellular-reactions; Vasoactive-agents; Chronic-inflammation; Immune-reaction; Cardiovascular-system-disorders; Pathology; Physiological-effects; Cytology; Cytotoxic-effects; Leukocytes; Proteins; Genetic-factors; Biological-effects; Biological-systems; Diseases
Berran Yucesoy, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Road, Morgantown, WV 26505-2888, USA
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Endothelium: molecular aspects of metabolic disorders