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Updated: May 7, 2026
Murine Cervical Heart Transplantation Model Using a Modified Cuff Technique
Published on: October 12, 2014
Short communications: Endothelin-1 in cardiac allograft vasculopathy
George R Abraham1, Anthony P Davenport2, Stephen P Hoole1
1Royal Papworth Hospital NHS Foundation Trust, Papworth Road, Cambridge Biomedical Campus, Cambridge CB2 0AY, United Kingdom of Great Britain and Northern Ireland; Experimental Medicine and Immunotherapeutics, University of Cambridge, Level 6, Addenbrooke's Centre for Clinical Investigation (ACCI), Box 110, Addenbrooke's Hospital, Cambridge, CB2 0QQ, United Kingdom of Great Britain and Northern Ireland.
Insights
Cardiac allograft vasculopathy (CAV) in heart transplant patients is linked to increased Endothelin-1 (ET-1) release. Higher ET-1 levels correlate with intimal thickening, suggesting a role in CAV development.
Area of Science:
- Cardiology
- Transplantation Immunology
- Vascular Biology
Background:
- Cardiac allograft vasculopathy (CAV) is a primary cause of mortality post-heart transplantation.
- Endothelin-1 (ET-1), a peptide from vascular endothelium, has potent vasoconstrictive properties and is implicated in CAV pathogenesis.
Purpose of the Study:
- To investigate the trans-myocardial gradient (TMG) of ET-1 in heart transplant recipients.
- To correlate ET-1 TMG with angiographic and intravascular imaging features of CAV.
Main Methods:
- Assessed ET-1 TMG (coronary sinus minus coronary artery concentration) in heart transplant patients.
- Utilized Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT) to evaluate CAV severity and intimal thickness.
- Correlated ET-1 TMG with IVUS/OCT findings and patient survival.
Main Results:
- More severe CAV (IVUS Stanford Grade IV) showed significantly higher ET-1 TMG (indicating net release) compared to less severe grades (p=0.01).
- ET-1 TMG positively correlated with intimal thickness measured by both IVUS (p=0.02) and OCT (p<0.0001).
- Deceased patients exhibited net ET-1 release, unlike surviving patients (p=0.01).
Conclusions:
- Increased ET-1 release in the coronary circulation is associated with intimal thickening in CAV.
- These findings suggest that elevated ET-1 may facilitate the development and progression of cardiac allograft vasculopathy.
Introduction:
Cardiac allograft vasculopathy (CAV) is a leading cause of death following heart transplant. Endothelin-1 (ET-1) is a highly potent vasoconstrictor peptide derived from the vascular endothelium with multiple biological actions known to be relevant for CAV. We assessed the trans-myocardial gradient (TMG: coronary sinus minus coronary artery concentration: negative = extraction, positive = secretion) of ET-1 in heart transplant patients to determine correlations with angiographic, Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT) features of CAV.
Results:
Vessels with more severe CAV demonstrated significantly higher (more positive) ET-1 TMG (IVUS Stanford Grade IV: -0.05 [-0.21, 0.13] pg/ml versus Stanford Grade I-III: -0.31 [-0.64, -0.11] pg/ml, p = 0.01). ET-1 TMG was positively correlated with mean intimal thickness on both IVUS and OCT (IVUS: Kendall's tau-b = 0.254, p = 0.02 and OCT: Kendall's tau-b = 0.344, p < 0.0001). Patients who died had net ET-1 release compared with surviving patients (died: 0.21 [0.19-0.24] versus surviving: -0.28 [-0.52, -0.17], p = 0.01).
Conclusion:
In heart transplant patients, coronary arteries with more intimal thickening are associated with a higher (more positive) trans-myocardial gradient of ET-1, suggesting that up-regulated ET-1 release in the coronary circulation may be permissive for the development of CAV.
