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Levels of circulating adhesion molecules in congestive heart failure and after heart transplantation
A K Andreassen1, I Nordøy, S Simonsen
1Section of Cardiology, Medical Department B, University of Oslo, Norway.
Insights
Inflammation plays a key role in heart failure and coronary artery disease after heart transplants. Post-transplant, adhesion molecule levels indicate ongoing immune activation, potentially driving long-term complications.
Area of Science:
- Cardiology
- Immunology
- Transplantation Medicine
Background:
- Congestive heart failure (CHF) and coronary artery disease (CAD) post-heart transplantation (HT) may involve immunologic and inflammatory processes.
- Adhesion molecules on endothelial cells, leukocytes, and platelets are critical in these interactions.
Purpose of the Study:
- To measure serum levels of soluble adhesion molecules (VCAM-1, P-selectin, E-selectin) in CHF patients and controls.
- To track these levels in patients for up to two years after heart transplantation.
Main Methods:
- Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), sP-selectin, and sE-selectin were measured.
- Measurements were taken in 34 severe CHF patients and 20 healthy controls.
- Serial measurements were performed on 20 post-HT patients for up to 2 years.
Main Results:
- All three adhesion molecules (CAMs) were elevated in CHF patients compared to controls.
- Post-HT, sE-selectin normalized, sVCAM-1 decreased but remained elevated, and sP-selectin remained persistently high.
- Persistent elevations in sP-selectin and sVCAM-1 correlated with elevated tumor necrosis factor-alpha, independent of rejection or infection.
Conclusions:
- Immunologic and inflammatory processes are integral to CHF pathogenesis.
- Persistent elevation of CAMs and TNF-alpha post-HT suggests ongoing immune activation.
- This chronic immune activation may contribute to the development of CAD after heart transplantation.
Abstract:
Recent reports suggest a role for immunologic and inflammatory processes in the pathogenesis of congestive heart failure (CHF) and accelerated coronary artery disease (CAD) after heart transplantation (HT). The interaction between endothelial cells, leukocytes, and platelets involving various adhesion molecules may be of particular importance. We therefore measured serum levels of soluble(s) vascular cell adhesion molecule-1 (VCAM-1), sP-selectin, and sE-selectin in 34 patients with severe CHF (23 with CAD and 11 with idiopathic dilated cardiomyopathy) and in 20 healthy controls. Twenty of the patients were followed with serial measurements of these circulating adhesion molecules (CAMs) for up to 2 years after HT. Levels of all 3 CAMs were significantly elevated in patients with CHF compared with controls irrespective of the etiology of heart failure, with particularly high concentrations of sVCAM-1. After HT, different patterns in CAMs were found over time. Whereas there was a normalization of sE-selectin levels after HT, concentrations of sVCAM-1 also declined, but without normalization. In contrast, sP-selectin levels were persistently elevated, with the highest concentrations at the end of the study period. The persistent elevation of sP-selectin and the lack of normalization of sVCAM-1 levels were associated with persistently raised serum levels of tumor necrosis factor-alpha, and these findings were not related to either acute episodes of allograft rejection or intercurrent infections. These results support the notion that immunologic and inflammatory processes are important features of CHF. Furthermore, the persistently elevated levels of CAMs and tumor necrosis factor-alpha found up to 2 years after HT may reflect a state of persistent immune activation in these patients, possibly involved in the development of CAD after HT.