Endothelin: 30 Years From Discovery to Therapy

Area of Science:

• Biochemistry
• Physiology
• Pharmacology

Background:

• Endothelin-1 (ET-1), discovered in 1987, is a potent vasoconstrictor with diverse physiological roles.
• Over 30,000 articles highlight ET-1's involvement in numerous biological processes and diseases.
• This has spurred the development of endothelin receptor antagonists (ERAs) as therapeutics.

Observation:

• ET-1 significantly contributes to cardiovascular diseases like hypertension, preeclampsia, atherosclerosis, and heart failure.
• ET-1 also plays a role in diabetic kidney disease, pulmonary arterial hypertension, cancer, immune disorders, and neurological conditions.
• Specific conditions like MINOCA and Takotsubo syndrome are linked to ET-1's effects.

Findings:

• Clinical trials have evaluated ERAs for various ET-1-mediated diseases.
• The review summarizes ET-1's role in genetics, physiology, and disease pathology.
• ET-1's involvement in autoimmune diseases, including ET_A autoantibodies in allograft rejection, is discussed.

Implications:

• Targeting endothelin receptors with ERAs, DARAs, or novel biologics may reverse chronic diseases.
• Future research will determine if endothelin receptor blockade improves patient outcomes and quality of life.
• Therapeutic strategies targeting the endothelin system offer potential for managing complex noncommunicable diseases.