Circulating Apoptotic Endothelial Cells and Apoptotic Endothelial Microparticles Independently Predict the Presence of Cardiac Allograft Vasculopathy

Study Questions:

Do biomarkers of endothelial cell injury and repair identify transplant patients with coronary allograft vasculopathy (CAV)?


This was a single-center cohort study of 52 patients who were 5-15 years post-cardiac transplant. Flow cytometry was used to measure endothelial progenitor cells (EPCs), circulating endothelial cells (CECs), and endothelial microparticles. CAV was defined as the presence of International Society of Heart and Lung Transplantation (ISHLT) grades CAV1-3 on angiogram. Healthy controls were used to establish biomarker reference values and transplant patients without evidence of CAV on angiogram served as transplant controls.


Compared with healthy, nontransplant controls, the number of circulating endothelial cells and apoptotic endothelial cells was higher in transplant patients (n = 52) overall. There were 30 transplant patients with CAV and 22 without. CAV patients were older, had older donor hearts, and there was a trend toward more everolimus use. Patients with CAV had a greater number of apoptotic CECs and circulating endothelial microparticles than patients without CAV (all p < 0.05). In addition to older age and higher serum creatinine, the number of apoptotic CEC (odds ratio, 4.3 [1.4-13.5]) and apoptotic endothelial microparticles (odds ratio, 5.3 [1.4-20]) were associated with the presence of CAV after transplant.


The authors concluded that the presence of apoptotic CEC and apoptotic endothelial microparticles are associated with CAV in patients with cardiac transplant.


The authors explained that there is a fine balance between endothelial cell death and repair. Immunologic injury, as occurs with chronic rejection in the form of CAV, can upset this balance. Apoptotic CEC and microparticles signal endothelial injury and cell activation and/or apoptosis. While the number of CECs is higher in transplant patients, in general, they are substantially higher in those with CAV. More studies are needed, but this certainly could be an interesting tool to assist in early CAV diagnosis and response to therapy.

Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant

Keywords: Lung Transplantation, Heart-Lung Transplantation, Heart Diseases, Chlorambucil, Reference Values, Heart Failure, Creatinine, Sirolimus, Cell Death, Endothelial Cells, Heart Transplantation

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