Estrogen-replacement therapy promotes angiogenesis after acute myocardial infarction by enhancing SDF-1 and estrogen receptor expression.

Although observational data suggest that estrogen-replacement therapy (ERT) may confer cardioprotection, estrogen's putative protective role has been challenged. This study investigated the effect of estradiol on peripheral blood stem cells and angiogenesis after acute myocardial infarction and potential mechanisms of estrogen's pro-angiogenesis effect. An ovariectomized rat acute myocardial infarction (AMI) model was established by ligation of the left anterior descending coronary followed by delivery of varying doses of estradiol benzoate. Serum estradiol levels were assessed by radioimmunoassay. Expression levels of alpha and beta estrogen receptor (ER) proteins in myocardium were determined by Western blotting. CD34(+) cells in myocardium at 24 h and in peripheral blood 1, 3 and 7 days after AMI were measured by immunohistochemistry and flow cytometry, respectively. Stromal cell-derived factor (SDF-1) expression and capillary density in myocardium were detected by immunohistochemistry. In ovariectomized rats, ERT significantly increased estradiol levels and up-regulated ER-alpha and -beta expression relative to untreated controls. Furthermore, ERT elevated the number of CD34(+) cells in peripheral blood and myocardium, increased SDF-1 expression, and increased capillary density 4 weeks after AMI. Therefore, our data suggest that estrogen can promote the mobilization and homing of bone marrow stem cells into the myocardium and can increase capillary density in myocardium after AMI. The pro-angiogenesis effect of ERT is associated with enhanced SDF-1 and ER-alpha and -beta expression in myocardium after AMI.