Endothelin-1 Dynamics in Cardiovascular Diseases

Endothelin-1 (ET-1) is a potent 21-amino-acid peptide synthesised by endothelial cells that exerts vasoconstrictive, proliferative and pro-inflammatory effects through activation of ET_A and ET_B receptors. In physiological states, ET-1 contributes to vascular tone and sodium–water homeostasis. In cardiovascular pathology, dysregulated ET-1 production and receptor signalling underpin arterial hypertension, heart failure, myocardial ischaemia, pulmonary hypertension and vascular remodelling. Chronic elevations of ET-1 and its precursor fragments (big ET-1, C-terminal pro-endothelin-1) correlate with adverse clinical outcomes, reflecting both endothelial dysfunction and maladaptive tissue repair. Recent mechanistic studies have elucidated interactions between ET-1 signalling and neurohormonal axes, including the renin–angiotensin system and sympathetic drive, as well as cross-talk with inflammatory mediators. Measurement of ET-1 or its stable precursors in plasma provides prognostic information, guides risk stratification and may identify patients likely to benefit from targeted therapies. Therapeutic modulation of the endothelin axis—through receptor antagonists or agents with off-target effects on ET-1 pathways—holds promise for attenuating vascular remodelling, reducing heart failure progression and improving long-term outcomes. The global burden of ET-1–driven cardiovascular disease underlines the need for integrated biomarker strategies and novel interventions that restore vascular homeostasis while limiting organ fibrosis and dysfunction.

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Endothelin-1 Dynamics in Cardiovascular Diseases publication trend

The graph below shows the total number of articles in endothelin-1 dynamics in cardiovascular diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Endothelin-1: 21-amino-acid vasoactive peptide produced by endothelial cells that regulates vascular tone and cellular proliferation.

Big Endothelin-1: 39-amino-acid precursor to endothelin-1 that serves as a stable marker of endothelin synthesis.

C-terminal pro-Endothelin-1 (CT-proET-1): Stable fragment derived from the endothelin-1 precursor used as a prognostic biomarker.

ET_A receptor: G-protein-coupled receptor mediating vasoconstriction and pro-proliferative effects of endothelin-1.

Left Ventricular Reverse Remodelling (LVRR): Improvement in ventricular structure and function characterised by increased ejection fraction and reduced chamber size.

SGLT2 inhibitor: Class of antidiabetic agents that modulate renal glucose reabsorption and exhibit cardiovascular protective effects.

References

1. Endothelin-1, Outcomes in Patients With Heart Failure and Reduced Ejection Fraction, and Effects of Dapagliflozin: Findings From DAPA-HF. Circulation (2023).
2. Big Endothelin-1 as a Predictor of Reverse Remodeling and Prognosis in Dilated Cardiomyopathy. Journal of Clinical Medicine (2023).
3. Predictive Value of Plasma Big Endothelin-1 in Adverse Events of Patients With Coronary Artery Restenosis and Diabetes Mellitus: Beyond Traditional and Angiographic Risk Factors. Frontiers in Cardiovascular Medicine (2022).