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The endothelium in clinical cardiac transplantation
Serban C Stoica1, Martin Goddard, Stephen R Large
1The Cardiothoracic Transplant Unit Papworth Hospital, Cambridge, United Kingdom.
Insights
Cardiac endothelium plays a critical role in heart transplant rejection and failure. Understanding its function from brain death through transplantation can improve patient outcomes and therapies.
Area of Science:
- Cardiovascular Science
- Transplantation Immunology
- Endothelial Biology
Background:
- Cardiac transplantation is a successful treatment for end-stage heart failure.
- Acute rejection, pump failure, and cardiac allograft vasculopathy remain significant challenges.
- The cardiac endothelium's role in these complications is increasingly recognized.
Purpose of the Study:
- To review the multifaceted roles of the cardiac endothelium in heart transplantation.
- To discuss current diagnostic and therapeutic strategies targeting endothelial function.
Main Methods:
- Literature review of endothelial cell biology and immunology in cardiac transplantation.
- Analysis of the endothelium's interaction with inflammatory, immune, and vascular systems.
- Examination of endothelial priming during brain death and subsequent injury phases.
Main Results:
- Brain death initiates an inflammatory response that primes the cardiac endothelium for injury.
- The endothelium acts as a crucial interface for inflammatory cell infiltration.
- Endothelial interactions with complement, coagulation, and immune cells are central to transplant complications.
Conclusions:
- Targeting endothelial dysfunction offers potential for improved cardiac transplant outcomes.
- Further understanding of endothelial roles can lead to novel therapeutic interventions.
- Comprehensive strategies addressing endothelial health are vital for long-term transplant success.
Abstract:
Cardiac transplantation is the most successful therapy for refractory heart failure, but clinical transplantation is still confronted with the problems of acute rejection and acute pump failure. The limiting factor in achieving prolonged survival remains cardiac allograft vasculopathy. In recent years it has become apparent that from brain death onward, the cardiac endothelium plays a key role in these acute and chronic events. Brain death is associated with an inflammatory response that primes the endothelium for cumulative injury during the subsequent stages of ischemic cold storage, reperfusion and allorecognition. As a structural and functional interface, the endothelium is the site at which inflammatory cells move from the bloodstream through the vessel wall into the parenchyma. The endothelium interacts with the complement system, the coagulation and inflammatory cascades, circulating leukocytes, the immune system, the smooth muscle in the vessel wall, and the surrounding matrix and cardiomyocytes. A better understanding of its many roles may lead to expansion of our therapeutic possibilities and better outcomes overall. This article reviews the possible roles of the endothelium in relation to cardiac transplantation, and discusses the diagnostic and therapeutic modalities that are available to date.