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Endothelin in Pathology |
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Increased circulating levels of endothelin (ET) have been observed in patients with pulmonary arterial hypertension (PAH), a life-threatening disease. 1 The diverse effects of ET include vasoconstriction, 2,3 vascular hypertrophy, 2 cell proliferation, 4 fibrosis, 4,5 and inflammation. 6,7 |
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*Statements are based on observations reported from in vitro or animal trials.
The clinical significance in humans is unknown. |
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ET receptors promote different effects depending on the cell type on which they are found. For instance, ETB receptors promote vasoconstriction and cell proliferation when found on smooth muscle cells, but vasodilation when found on endothelial cells. In pathology, these differences are amplified due to up- and downregulation.5,8 |
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Because ET is expressed by and its receptors are located on a wide variety of cell types throughout the body, the effects of excess ET in pathology are far-reaching and numerous. Areas of study include the vessels, the heart, the lungs, the skin, the kidneys,
and the brain.5,7 |
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REFERENCES |
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2. |
Rich S, McLaughlin VV. Pulmonary hypertension. In: Libby P, Bonow RO, Mann DL, Zipes DE. Braunwald's Heart Disease. 2 vols. 8th ed. Philadelphia, PA: Saunders Elsevier; 2008:1883–1914. |
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Miyauchi T, Masaki T. Pathophysiology of endothelin in the cardiovascular system. Annu Rev Physiol. 1999;61:391–415. |
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4. |
Davie N, Haleen SJ, Upton PD, et al. ET(A) and ET(B) receptors modulate the proliferation of human pulmonary artery smooth muscle cells. Am J Respir Crit Care
Med. 2002;165:398–405. |
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5. |
Kim NH, Rubin LJ. Endothelin in health and disease: endothelin receptor antagonists in the management of pulmonary artery hypertension. J Cardiovasc Pharmacol Ther. 2002;7:9–19. |
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6. |
Muller DN, Mervaala EM, Schmidt F, et al. Effect of bosentan on NF-kappaB, inflammation, and tissue factor in angiotensin II-induced end-organ damage. Hypertension. 2000;36:282–576. |
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7. |
Kedzierski RM, Yanagisawa M. Endothelin system: the double-edged sword in health and disease. Annu Rev Pharmacol Toxicol. 2001;41:851–876. |
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8. |
Rae GA, Henriques MGMO. Endothelins in inflammation. In Said SI, ed. Proinflammatory and Antiinflammatory Peptides. New York: Marcel Dekker Inc; 1998:163–202. |
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9. |
Shi-Wen X, Denton CP, Dashwood MR, et al. Fibroblast matrix gene expression and connective tissue remondeling: role of endothelin-1. J Invest Dermatol. 2001;116:417–1425. |
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10. |
Levin ER. Endothelins. N Engl J Med. 1995;333:359–363. |
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