Expression of estrogen receptor sub-types alpha and beta in acute and chronic cardiac allograft vasculopathy

The vasculoprotective effects of estrogen are well-established not only in women with age-related atherosclerosis, but also after experimental vascular injury and in chronic allograft vasculopathy. Evidence exists that the newly discovered estrogen receptor (ER) beta, rather than the classical ERalpha is related to the vasculoprotective effect. Here we investigate whether and to what extent the two ERs are expressed in cardiac allografts in the rat and human in native state and during acute and chronic rejection.

Rat cardiac allografts were performed from male DA (AG-B4, RT1(a)) to male WF (AG-B2, RT1(v)) strain and syngeneic transplants from DA to DA strain; human male-to-male heart allograft endomyocardial biopsies came from our biopsy files.

Under in situ hybridization, ERbeta mRNA was prominently expressed in rat vessels and stroma, whereas ERalpha mRNA was present in low levels only. In immunohistochemistry, 2 ERbeta-specific antibodies stained rat and human vessels and stroma, whereas only a weak or no signal was obtained with 2 ERalpha-specific antibodies. Interestingly, the mRNA and protein expression levels in the rat carried only a weak correlation with the intensity of acute rejection, i.e., was not related to the intensity of inflammation.

Our results demonstrate that ERbeta is the predominant ER in rat and human cardiac allografts, and suggest that, unless additional ERs are identified, the vasculoprotective effects of estrogen derivatives in cardiac allograft vasculopathy are mediated by ERbeta rather than by the classical ERalpha.