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Endothelin

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Abstract

Endothelin-1 is the most potent vasoconstrictor agent currently identified, and it was originally isolated and characterized from the culture media of aortic endothelial cells. Two other isoforms, termed endothelin-2 and endothelin-3, were subsequently identified, along with structural homologues isolated from the venom of Actractapis engaddensis known as the sarafotoxins. In this review, we will discuss the basic science of endothelins, endothelin-converting enzymes, and endothelin receptors. Only concise background information pertinent to clinical physician is provided. Next we will describe the pathophysiological roles of endothelin-1 in pulmonary arterial hypertension, heart failure, systemic hypertension, and female malignancies, with emphasis on ovarian cancer. The potential intervention with pharmacological therapeutics will be succinctly summarized to highlight the exciting pre-clinical and clinical studies within the endothelin field. Of note is the rapid development of selective endothelin receptor antagonists, which has led to an explosion of research in the field.

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Acknowledgments

Due to restricted space, we apologize to those whose work is not described in this review. Work from our laboratory that is cited in this review has been supported by grants from the Merck Company Foundation, Banyu Fellowship in Cardiovascular Medicine, the National Institutes of Health (NIH: DK080640), and the Japan Society for the Promotion of Science (JSPS: S-10707). We thank Charisse Montgomery for her editorial support. Y. Kawanabe is the recipient of the Merck Company Foundation and Banyu fellowship awards in cardiovascular medicine.

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  1. Department of Neurosurgery, Otsu Municipal Hospital, 2-9-9 Motomiya, Otsu, Shiga, 520-0804, Japan

    Yoshifumi Kawanabe

  2. Department of Pharmacology, The University of Toledo, Toledo, OH, 43606, USA

    Surya M. Nauli

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  1. Yoshifumi Kawanabe
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  2. Surya M. Nauli
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Correspondence to Yoshifumi Kawanabe.

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Kawanabe, Y., Nauli, S.M. Endothelin. Cell. Mol. Life Sci. 68, 195–203 (2011). https://doi.org/10.1007/s00018-010-0518-0

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  • DOI: https://doi.org/10.1007/s00018-010-0518-0

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