Inflammatory endothelin

Lattmann T, Hein M, HOrber S, Ortmann J, et al. 2005. Activation of pro-inflammatory and antiinflammatory cytokines in host organs during chronic allograft rejection Role of endothelin receptor signaling. Am J Transplant. 5 1042-1049. 

The thrombotic disorders include atherothrombosis, endothelial dysfunction, hypercoagulable states, and the thrombophilias. Atherothrombosis or atherosclerosis is a systemic disease of the vessel wall occuring in the aorta, carotid, coronary, and peripheral arteries. The associated inflammatory response is mediated by macrophages and T-lymphocytes with continued smooth muscle cell proliferation, The levels of endothelin-l (ET-I), an extremely potent... 

Anti-inflammatory effects Prevents downregulation of endothelial nitric oxide synthase Decreased synthesis of endothelin-1 Reduced endothelial and soluble adhesion molecules... 

Givertz MM, Colucci WS, New targets for heart failure therapy endothelin, inflammatory cytokines, and oxidative stress, Lancet I 998 352(suppl I ) S 134-SI 38. 

Johnson AG, Nguyen TV, Owe-Young R, Williamson DJ, Day RO. Potential mechanisms by which nonsteroidal anti-inflammatory drugs elevate blood pressure the role of endothelin-1. J Hum Hypertens 1996 10(4) 257-61. 

The endothelin peptides are potent vasoconstrictors that may be involved in heart failure pathophysiology through a number of mechanisms. Endothelin-1 (FT-1), the best characterized of these peptides, is synthesized by endothelial and vascular smooth muscle cells, with the release of ET-1 enhanced by NE, angiotensin II, and inflammatory cytokines. Like other peptides and hormones described earlier, ET-1 plasma concentrations are elevated in heart failure and... 

Endothelins and their receptors may be induced within the tumor microenvironment by hypoxia via stabilization of HIF-la as well as by inflammatory cytokines and chemokines [44]. These studies imply that multiple factors within the tumor microenvironment upregulate endothelin expression in local tumor regions, which in turn induces CCR7 expression by tumor cells. Interestingly, another chemokine receptor (i.e., CXCR4) associated with cancer cells is also induced by hypoxia via HIF-1-dependent mechanisms [19], suggesting that hypoxia may be an inducer of a variety of chemokine receptors. (See Chapter 3.)... 

Endothelin receptor antagonists Swine Vasodilator Coronary arteries (right), coronary groove, and atrium Medial hemorrhage and necrosis, with mixed inflammatory cell infiltrates in the adventitia and media McDuffie et al (2006)... 

Endothelin-1, a peptide initially purified from porcine aortic endothelial cells, has been shown to be expressed by human pneumocytes type II in lung fibrosis (Giaid et al. 1993), by rat pneumocytes II (Crestani et al. 1994), and a cell line derived from rat pneumocytes II (L2 Markevitz et al. 1995). ET-1 has potent vascular and bronchial smooth muscle cell constrictor properties, acts as a mitogen for different cell types, such as fibroblasts or smooth muscle cells (Battistini et al. 1993), and is involved in the modulation of the inflammatory response through a direct effect on alveolar macrophages (Na-GASE et al. 1990) or mast cells (Ehrenreich et al. 1992). ET-1 production is inhibited by IL-ip (Odoux et al. 1997). IL-ip effect was dependent on protein synthesis, was partially prevented by indomethacin, and was totally prevented by dexamethasone. 

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