Related Experiment Videos
Heart allograft endothelial cell dysfunction. Cause, course, and consequences
M Weis1, S Pehlivanli, W von Scheidt
1Universitätsklinikum Grosshadern Medizinische Klinik und Poliklinik I Marchioninistrasse 15 81377 München, Germany. mweis@med1.med.uni-muenchen.de
Insights
Coronary endothelial dysfunction, a common complication after heart transplantation, is distinct from intimal thickening and predicts cardiac events. Early endothelial protection is crucial for long-term allograft health.
Area of Science:
- Cardiovascular Science
- Transplantation Immunology
- Endothelial Biology
Background:
- Allograft coronary endothelial cells act as stimulators and targets in allogeneic immune responses.
- Endothelial cell injury post-transplantation leads to activation, dysfunction, and altered molecule expression.
- Coronary endothelial vasomotor dysfunction affects 20-30% in the first year and 30-40% long-term post-transplant.
Purpose of the Study:
- To investigate the role of coronary endothelial cells in allograft vasculopathy.
- To differentiate endothelial dysfunction from intimal thickness in allografts.
- To identify predictors and protective strategies for allograft endothelial dysfunction.
Main Methods:
- Analysis of endothelial cell function and molecule expression in allograft recipients.
- Assessment of intimal thickness and its correlation with endothelial dysfunction.
- Evaluation of early predictors like proinflammatory cytokines and endothelin.
Main Results:
- Endothelial dysfunction and intimal thickness are distinct entities in allograft vasculopathy.
- Proinflammatory cytokines and endothelin are early predictors of vasomotor dysfunction.
- Endothelial dysfunction predicts cardiac events in both transplant and non-transplant patients.
Conclusions:
- Early administration of endothelial-protective compounds is essential for preventing allograft endothelial dysfunction.
- Gene therapy, improved cardioplegia, and specific drug classes (statins, ACE inhibitors) show promise for protection.
Abstract:
Allograft coronary endothelial cells can serve as potent stimulators (antigen-presenting cells) as well as targets of allogeneic lymphocyte reactivity. Independent of the cause leading to endothelial cell injury after transplantation, endothelial cell activation and dysfunction occurs, associated with modification in endothelial cell-dependent molecule expression. The prevalence of coronary endothelial vasomotor dysfunction is approximately 20-30% during the first year, and 30-40% in the long-term follow-up. Importantly, no association is detectable between endothelial dysfunction and intimal thickness, suggesting two distinct entities of allograft vasculopathy. Early predictors of vasomotor dysfunction are proinflammatory cytokines and endothelin expression. Repetitive subendocardial ischemia during myocardial stress (due to microvascular dysfunction) may result in an impairment of left ventricular function. In non-transplant patients coronary endothelial dysfunction predicts cardiac events during long-term follow-up. It is reasonable that early administration of endothelial-protective compounds is necessary for protection of allograft endothelial dysfunction and vasculopathy during follow-up. The explanted donor heart may offer a potential for gene therapy techniques including modification of allograft phenotype and modulation of the host alloimmune response. Other protective strategies may include improvement of cardioplegic solutions and reperfusion strategies, recovery of the imbalance between vasoactive mediators, and treatment with HMG-CoA-reductase inhibitors and/or ACE inhibitors.