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

SIMPLE SUMMARY: In this review, we describe the basic functions of endothelin and related molecules, including their receptors and enzymes. Furthermore, we discuss the important role of endothelin in several cardiovascular diseases, the relevant clinical evidence for targeting the endothelin pathway, and the scope of endothelin-targeting treatments in the future. We highlight the present uses of endothelin receptor antagonists and the advancements in the development of future treatment options, thereby providing an overview of endothelin research over the years and its future scope. 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.