Cardiac allograft vasculopathy: a donor or recipient induced pathology?

Patricia Van Den Hoogen,Roel A De Weger,Manon M H Huibers,Joost P G Sluijter

doi:10.1007/s12265-015-9612-x

Patricia Van Den Hoogen, Roel A De Weger + Show 2 more

Open Access

https://doi.org/10.1007/s12265-015-9612-x

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Abstract

Cardiac allograft vasculopathy (CAV) is one of the main causes of late-stage heart failure after heart transplantation. CAV is characterized by concentric luminal narrowing of the coronary arteries, but the exact pathogenesis of CAV is still not unraveled. Many researchers show evidence of an allogeneic immune response of the recipient, whereas others show contrasting results in which donor-derived cells induce an immune response against the graft. In addition, fibrosis of the neo-intima can be induced by recipient-derived circulating cells or donor-derived cells. In this review, both donor and recipient sides of the story are described to obtain better insight in the pathogenesis of CAV. Dual outcomes were found regarding the contribution of donor and recipient cells in the initiation of the immune response and the development of fibrosis during CAV. Future research could focus more on the potential synergistic interaction of donor and recipient cells leading to CAV.

Highlights

Cardiac transplantation is often successfully applied in the treatment of end-stage heart failure [1]
Deficiency of donor PD-L1 leads to the secretion of IFN-γ and proliferation of alloreactive T-lymphocytes of the recipient, thereby promoting a recipient allo-immune response [46]. These findings show that PD-L1 expression on cardiac tissue or leukocytes of the donor is critical in the regulation of an allograft immune response in heart transplant recipients [45, 46]
Cardiac allograft vasculopathy (CAV) is a complex disease with an unrevealed pathogenesis

Summary

Introduction

Cardiac transplantation is often successfully applied in the treatment of end-stage heart failure [1]. The exact mechanism in which CAV is induced after heart transplantation is not elucidated, but it is known that both donor and recipient cells are involved [13]. The trigger of these responses (direct, indirect, and semi-direct pathways, Bautoimmunity^ and CMV infection) leads to the proliferation of smooth muscle cells (SMCs), accumulation of extracellular matrix and hyperplasia of the intima of the vessel wall (Fig. 2) [15, 22, 23].

Results

Conclusion