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Review
. 2022 May 16;11(5):759.
doi: 10.3390/biology11050759.

Endothelin and the Cardiovascular System: The Long Journey and Where We Are Going

Andreas Haryono  1   2 , Risa Ramadhiani  2 , Gusty Rizky Teguh Ryanto  2 , Noriaki Emoto  1   2
Affiliations
Review

Endothelin and the Cardiovascular System: The Long Journey and Where We Are Going

Andreas Haryono et al. Biology (Basel). .

Abstract

Endothelin was first discovered more than 30 years ago as a potent vasoconstrictor. In subsequent years, three isoforms, two canonical receptors, and two converting enzymes were identified, and their basic functions were elucidated by numerous preclinical and clinical studies. Over the years, the endothelin system has been found to be critical in the pathogenesis of several cardiovascular diseases, including hypertension, pulmonary arterial hypertension, heart failure, and coronary artery disease. In this review, we summarize the current knowledge on endothelin and its role in cardiovascular diseases. Furthermore, we discuss how endothelin-targeting therapies, such as endothelin receptor antagonists, have been employed to treat cardiovascular diseases with varying degrees of success. Lastly, we provide a glimpse of what could be in store for endothelin-targeting treatment options for cardiovascular diseases in the future.

Keywords: coronary artery disease; endothelin; endothelin receptor antagonist; heart failure; hypertension; pulmonary hypertension.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Biosynthesis of endothelin.
Figure 2
Figure 2
Sites and mechanism of action of endothelin.
Figure 3
Figure 3
Pharmacologic mechanism of biased G-protein-coupled receptor signaling.
See this image and copyright information in PMC

References

    1. Furchgott R.F., Vanhoutte P.M. Endothelium-derived relaxing and contracting factors. FASEB J. 1989;3:2007–2018. doi: 10.1096/fasebj.3.9.2545495. - DOI - PubMed
    1. Barton M., Yanagisawa M. Endothelin: 30 years from discovery to therapy. Hypertension. 2019;74:1232–1265. doi: 10.1161/HYPERTENSIONAHA.119.12105. - DOI - PubMed
    1. Hickey K.A., Rubanyi G., Paul R.J., Highsmith R.F. Characterization of a coronary vasoconstrictor produced by cultured endothelial cells. Am. J. Physiol. Cell Physiol. 1985;17:C550–C556. doi: 10.1152/ajpcell.1985.248.5.C550. - DOI - PubMed
    1. O’Brien R.F., Robbins R.J., McMurtry I.F. Endothelial cells in culture produce a vasoconstrictor substance. J. Cell. Physiol. 1987;132:263–270. doi: 10.1002/jcp.1041320210. - DOI - PubMed
    1. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332:411–415. doi: 10.1038/332411a0. - DOI - PubMed

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