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Cardiac allograft vasculopathy after cardiac transplantation and hormone therapy: positive effects?
Volkmar Lange1, Andre Renner, Martina Sagstetter
1Department of Cardiac and Thoracic Surgery, University of Wuerzburg, Germany.
Insights
Hormone replacement therapy with 17beta-estradiol after heart transplantation does not improve cardiac allograft vasculopathy (CAV) and may worsen heart function and increase fibrosis.
Area of Science:
- Immunology
- Endocrinology
- Transplantation Science
Background:
- Hormone replacement therapy (HRT) post-transplantation is controversial.
- Its impact on cardiac allograft vasculopathy (CAV) and allograft function remains unclear.
Purpose of the Study:
- To investigate the long-term effects of 17beta-estradiol and Coumestrol on CAV and fibrosis.
- To evaluate the influence of these compounds on cardiac allograft function.
Main Methods:
- Utilized an ovariectomized female heterotopic chronic allograft model (LEW-F344).
- Administered 17beta-estradiol and synthetic phytoestrogen Coumestrol.
- Assessed intimal thickening, perivascular immune reaction, fibrosis, and cardiac function 150 days post-transplantation.
Main Results:
- No significant effect of estrogen on intimal thickening was observed.
- Both 17beta-estradiol and Coumestrol reduced perivascular immune reactions, but this did not impact CAV severity.
- 17beta-estradiol treatment led to the greatest decline in heart function and increased fibrosis.
Conclusions:
- 17beta-estradiol does not offer positive effects on CAV after heart transplantation.
- 17beta-estradiol treatment negatively impacts cardiac allograft function and exacerbates fibrosis.
- This study is the first to demonstrate long-term negative effects of 17beta-estradiol post-heart transplantation.
Background:
There is a great deal of controversy surrounding the issue of hormone replacement therapy after transplantation. The question whether or not this therapy has effects in cardiac allograft vasculopathy (CAV), the Achilles heel of cardiac transplantation or other unique aspects of allograft function is still unknown.
Methods:
We investigated the long-term effect of 17beta-estradiol as well as phytoestrogen Coumestrol, a synthetically produced phytoestrogen, on the development of CAV and the degree of fibrosis in an ovariectomized female heterotopic chronic allograft model (LEW-F344).
Results:
We found that, 150 days after transplantation, no significant effect of estrogen application on intimal thickening of coronary arteries was observed. 17beta-estradiol and phytoestrogen Coumestrol did significantly reduce the perivascular immune reaction. However, the immune effect had no consequence on the intensity of CAV. Although neither 17beta-estradiol nor phytoestrogen Coumestrol revealed a positive effect on CAV, the group of animals treated with 17beta-estradiol showed the highest decline in heart function and the most distinct fibrosis.
Conclusions:
17beta-estradiol does not affect CAV positively, but worsens cardiac allograft function and leads to increased fibrosis. This is the first study showing a negative effect of 17-beta-estradiol after heart transplantation in the long term.
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