Estrogen reduces neointima formation independent of osteopontin expression in mouse carotid ligation model of vascular injury

This study tested the hypothesis that 17β-estradiol (E2) reduces neointima formation after vascular injury via a mechanism that is dependent on modulation of OPN expression. Mice with homozygous deletion of OPN (OPN -/-) were studied. Males were studied intact (INT), and females were studied INT or following ovariectomy (OVX) and implantation of E2 or vehicle (V). Injured vessels were examined 28 days after carotid ligation injury for cross-sectional media and neointima areas. There was a marked sexual dimorphism in neointima formation in the OPN-/- mice with INT females having a >70% reduction in neointima formation compared to INT males (see graph). The sexually dimorphic response was attenuated by OVX, with V treated females having no significant difference in neointima formation compared to INT males. E2 replacement in OVX females restored the sexually dimorphic response with a 58% reduction in neointima formation compared to OVX+V females. There was no difference in media area among the groups. These results demonstrate that E2 has vasoprotective effects following vascular injury that are independent of osteopontin expression. See Figure 1.