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Endothelin receptor polymorphisms in the cardiovascular system: potential implications for therapy and screening

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Abstract

Since its discovery in 1988, the endothelin system has been employed in multiple physiological and pathological roles. Endothelin-1 (ET-1) is not only a major regulator of vascular tone and cardiac contractility but also exerts mitogenic effects and is involved in inflammatory responses. ET-1 acts via two endothelin receptors located mainly on smooth muscle and endothelial cells through complex intracellular pathways differing between receptors and cell types. Polymorphisms of the endothelin receptor A have been associated not only with the risk in pulmonary arterial hypertension (PAH), systolic heart failure and systemic hypertension but are also of prognostic significance in dilated cardiomyopathy. Polymorphisms of endothelin receptors might lead to altered endothelin signaling and influence the response to endothelin receptor antagonist therapy in PAH in light of pharmacogenetics. This review will summarize the role of ET-1 within major cardiovascular pathologies and discuss endothelin receptor polymorphisms with special emphasis on potential therapeutic and screening implications.

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Authors and Affiliations

  1. Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, 1400 Pelham Parkway South, Bronx, NY, 10461, USA

    Luise Holzhauser

  2. Department of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, 1825 Eastchester Road, Bronx, NY, 10461, USA

    Ronald Zolty

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  1. Luise Holzhauser
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  2. Ronald Zolty
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Correspondence to Luise Holzhauser.

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Holzhauser, L., Zolty, R. Endothelin receptor polymorphisms in the cardiovascular system: potential implications for therapy and screening. Heart Fail Rev 19, 743–758 (2014). https://doi.org/10.1007/s10741-014-9426-y

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