Estrogen Regulation of Endothelial and Smooth Muscle Cell Migration and Proliferation

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Abstract
Objective— Restenosis is a major limitation of percutaneous coronary intervention. Migration and proliferation of vascular cells remain a cornerstone in neointimal formation. The cardioprotection of estrogen is well recognized, but the intracellular mechanisms related to these beneficial effects are not completely understood. Methods and Results— We investigated the effects of 17β-estradiol (17βE) on mitogen-activated protein kinase (MAPK) activity and the migration and proliferation of porcine aortic endothelial cells (PAECs) and porcine smooth muscle cells (PSMCs). Treatment with 17βE (10 −8 mol/L) abrogated p38 and p42/44 MAPK phosphorylation mediated by platelet-derived growth factor-BB as well as the migration and proliferation of PSMCs. In contrast, treatment with 17βE (10 −8 mol/L) induced the phosphorylation of p38 and p42/44 MAPK and the migration and proliferation of PAECs. Interestingly, the effects of 17βE on PSMCs and PAECs were reversed by selective estrogen receptor antagonists (tamoxifen, 4-OH-tamoxifen, and raloxifen). These results suggest that in PSMCs, 17βE inhibits chemotactic and mitogenic effects of platelet-derived growth factor-BB as well as p38 and p42/44 MAPK phosphorylation. In contrast, 17βE promotes in PAECs the phosphorylation of p42/44 and p38 MAPK as well as the migration and proliferation of these cells. Conclusions— Treatment with 17βE has a dual beneficial effect: the improvement of vascular healing and the prevention of restenosis after angioplasty.