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Updated: Apr 25, 2026
Mouse Model of Alloimmune-induced Vascular Rejection and Transplant Arteriosclerosis
Published on: May 17, 2015
Distinct phenotypes of cardiac allograft vasculopathy after heart transplantation: a histopathological study
Manon M H Huibers1, Aryan Vink1, Johannes Kaldeway1
1Department of Pathology, University Medical Center Utrecht, The Netherlands.
Insights
Cardiac allograft vasculopathy (CAV) after heart transplantation (HTx) presents in three histological phenotypes: inflammatory, smooth muscle cell-rich, and fibrotic. These CAV types correlate with transplant duration, recipient age, atherosclerosis, and infection risk.
Area of Science:
- Cardiology
- Transplantation Immunology
- Pathology
Background:
- Cardiac allograft vasculopathy (CAV) significantly impacts long-term survival following heart transplantation (HTx).
- Understanding CAV's underlying mechanisms is crucial for developing effective therapeutic strategies.
- This study aimed to explore histological CAV phenotypes and their clinical correlations.
Purpose of the Study:
- To classify histological phenotypes of cardiac allograft vasculopathy (CAV).
- To investigate the relationship between CAV phenotypes and clinical characteristics in heart transplant recipients.
- To elucidate the progression and remodeling associated with different CAV types.
Main Methods:
- Autopsy coronary cross-sections from 51 heart transplant (HTx) patients were analyzed.
- Three distinct histological CAV phenotypes (H-CAV 1-3) were identified based on intimal layer composition.
- Morphometric analysis was performed to assess intimal area and arterial remodeling.
Main Results:
- CAV was prevalent in 82% of HTx patients studied.
- Identified phenotypes included: normal (H-CAV 0), inflammatory (H-CAV 1), smooth muscle cell-rich (H-CAV 2), and fibrotic (H-CAV 3).
- H-CAV type significantly correlated with time post-transplantation, recipient age, atherosclerotic burden, and infection history. Higher H-CAV types showed increased intimal area with compensatory expansive arterial remodeling.
Conclusions:
- CAV is a progressive condition classifiable into inflammatory, smooth muscle cell-rich, and fibrotic phenotypes.
- These histological phenotypes are associated with key clinical factors including time since transplantation, recipient age, atherosclerosis, and infection.
- The findings provide insights into CAV pathogenesis and potential targets for intervention.
Introduction:
Long-term survival after heart transplantation (HTx) is hampered by cardiac allograft vasculopathy (CAV). Better understanding of the pathophysiological mechanisms of CAV might have considerable consequences for therapeutic approaches in the future. The aim of the present study was to investigate the histological phenotypes of CAV in relation with clinical patient characteristics.
Methods And Results:
Coronary cross-sections from 51 HTx patients were obtained at autopsy. CAV was observed in 42 patients (82%). Three histological CAV phenotypes were identified (H-CAV 1-3). No CAV (H-CAV 0) is as seen in normal coronary arteries; intimal thickening consisting of a layer of longitudinal oriented smooth muscle cells. In H-CAV 1 to 3 a second intimal layer is formed, on top of the longitudinal oriented smooth muscle cell layer, with predominantly mononuclear inflammatory infiltrate in loose connective tissue (H-CAV 1), smooth muscle cells in different orientation (H-CAV 2), or a fibrotic intimal lesion (H-CAV 3). H-CAV type was significantly related with time after transplantation, age at transplantation, the amount of atherosclerotic disease and the occurrence of infection. In addition, morphometric analysis revealed that higher H-CAV types have a relatively larger intimal area, that is compensated for by expansive arterial remodeling of the artery.
Conclusion:
CAV in an ongoing process that can be classified into three different phenotypes; inflammatory lesions, lesions rich of smooth muscle cells and fibrotic lesions. Our results suggest that these phenotypes are related to time after transplantation, age at transplantation, the amount of atherosclerotic disease and the occurrence of infection.
