Effects of estrogen on vascular inflammation: a matter of timing.

OBJECTIVE Our study aims to determine the role of time of menopause on vascular inflammation biomarkers and how it affects their modulation by estrogen and raloxifene in postmenopausal women. METHODS AND RESULTS Uterine arteries from 68 postmenopausal women were divided into 3 segments and cultured for 24 hours in tissue culture media containing 17β-estradiol (100 nmol/L), raloxifene (100 nmol/L), or vehicle. Assessment of arterial concentration of 13 inflammatory biomarkers was performed by multiplex immunobead-based assay. Aging per se has a positive correlation with the generation of several proinflammatory markers. Although short-term estradiol exposure correlates with lower expression of tumor necrosis factor-α, vascular endothelial growth factor, and interleukin-1β in all age groups, for most biomarkers aging was associated with a switch from a beneficial anti-inflammatory action by estrogen, at earlier stages of menopause, to a proinflammatory profile after 5 years past its onset. Raloxifene has no significant effect on the expression of all proinflammatory markers. Western blot analysis of estrogen receptor expression (estrogen receptor-α and estrogen receptor-β) showed that estrogen receptor-β increases with aging, and this increase has a positive correlation with the generation of several proinflammatory markers. CONCLUSIONS Aging alters estrogen-mediated effects on the modulation of inflammatory biomarkers in women. How aging affects estrogen responses on vascular inflammation is not clear, but our data show a positive association between increased estrogen receptor-β expression with aging and proinflammatory effects by estrogen.