***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective —17&bgr;-Estradiol ( E2 ) offers cardiovascular protection in young female animals and postmenopausal women . In contrast , r and omized trials of menopausal hormones performed in older women have shown harm or no cardiovascular benefit . We hypothesize that E2 effects on vascular inflammation are age dependent . Approach and Results —Young ( 10 weeks ) and aged ( 52 weeks ) female C57BL/6 mice were used as source for primary cultures of bone marrow – derived macrophages ( BMMs ) and vascular smooth muscle cells ( VSMCs ) . E2 pretreatment of cells derived from young mice attenuated C-reactive protein (CRP)–induced expression of inflammatory mediators . In contrast , E2 pretreatment of cells from aged mice did not alter ( BMMs ) or paradoxically exaggerated ( VSMCs ) inflammatory mediator response to CRP . Using E2 receptor ( ER ) knockout mice , we demonstrated that E2 regulates inflammatory response to CRP in BMMs via ER&agr ; and in VSMCs via ER&bgr;. BMMs derived from aged ( versus young ) mice expressed significantly less ER&agr ; mRNA and protein . A selective lig and of the novel ER GPR30 reproduced the E2 effects in BMMs and VSMCs . Unlike in young mice , E2 did not reduce neointima formation in ligated carotid arteries of aged CRP transgenic mice . Conclusions —E2 attenuates inflammatory response to CRP in BMMs and VSMCs derived from young but not aged mice and reduces neointima formation in injured carotid arteries of young but not aged CRP transgenic mice . ER&agr ; expression in BMMs is greatly diminished with aging . These data suggest that vasoprotective effects of E2 are age dependent and may explain the vasotoxic effects of E2 seen in clinical trials of postmenopausal women We have demonstrated that long-term 17β-estradiol attenuated fibrosis after myocardial infa rct ion , but recent evidence suggests that estrogen mediates more rapid cellular effects . RhoA has been shown to play a role in the control of myocardial fibrosis by regulating the actin-regulatory protein cofilin . We sought to eluci date whether RhoA activity regulates estradiol-induced fibrosis after infa rct ion in ovariectomized female rats . Twenty-four hours after coronary ligation , female Wistar rats were r and omized into control or estradiol treatment for 4 weeks starting from 2 weeks after bilateral ovariectomy . There were similar infa rct sizes among the infa rct ed groups . Myocardial fibrosis was significantly reduced , as measured by hydroxyproline content , Sirius Red staining and actin polymerization after administering estradiol . Estradiol treatment was associated with RhoA/Rho kinase inhibition evidence d by increased phosphorylation of RhoA and decreased phosphorylation of downstream factors including cofilin . Administration of PPT , a specific ERα agonist , or a membrane impermeable estrogen – albumin construct also inhibited cofilin phosphorylation , suggesting that cofilin phosphorylation is achieved through the recruitment of a membrane ERα . The ERβ-selective agonist , DPN , did not alter cofilin phosphorylation levels , but the ER antagonist , ICI 182,780 increased cofilin phosphorylation levels . G-15 ( an inhibitor of G-protein coupled estrogen receptor ) did not affect the phosphorylation as compared with estradiol alone . The inhibitor of Rho kinase , Y-27632 , attenuated cofilin phosphorylation levels , similar to the effect produced by estradiol . These results indicate that chronic use of estradiol after infa rct ion attenuates cardiac fibrosis by inhibiting RhoA/ROCK/cofilin pathway , which is exerted through membrane ERα-mediated receptor mechanism . Key MessagePostinfa rct ion was associated with increased cardiac fibrosis . Myocardial fibrosis was significantly reduced after administering estradiol (E2).Administration of the membrane ERα agonist PPT or E2-BSA  inhibited cofilin phosphorylation . Combination of E2 and Y-27632 did not enhance the attenuation of cofilin phosphorylation . Chronic use of E2 attenuated cardiac fibrosis by inhibiting the RhoA/ROCK/cofilin pathway via ERα BACKGROUND Environmental and genetic factors contribute to the development of complex diseases such as myocardial infa rct ion ( MI ) , the leading cause of death in men and women . Women develop MI approximately 10 years later than men , a difference that could be explained by the genes coding for the estrogen receptors . Single nucleotide polymorphisms ( SNPs ) in the ESR2 gene may affect susceptibility for MI in a sex-dependent manner . METHODS A nested case-control design was used to analyze 3 polymorphisms of the ESR2 gene and their associated haplotypes in 710 myocardial infa rct ion cases from the REGICOR ( Registre Gironí del Corazón ) study and 2379 controls r and omly selected in a representative population of a Spanish cross-sectional study . RESULTS The rs1271572 T allele was significantly more common in patients who developed MI ( P < 0.001 ) . No association was observed for rs1256049 or rs4986938 . Assuming a dominant model of inheritance , the association , as determined by logistic multivariate regression after adjustment for conventional cardiac risk factors , remained statistically significant in men [ odds ratio ( OR ) 1.65 , 95 % CI 1.18 - 2.30 ; P = 0.003 ) but not in women ( P = 0.754 ) . A very common haplotype encompassing the rs1271572 variant was also associated with the risk of MI in the overall population ( OR 1.41 , 95 % CI 1.06 - 1.87 ; P = 0.020 ) and in men ( OR 1.57 , 95 % CI 1.12 - 2.21 ; P = 0.009 ) . CONCLUSIONS The rs1271572 SNP T variant was associated with increased risk of MI in a Spanish population , and this association was found to be limited to men only . Sex differences in the genetic risk merit further investigation OBJECTIVE Hormone therapy ( HT ) has been suggested to improve vascular function and inflammation in menopausal women , although not consistently . We aim ed to investigate the effects of HT on endothelial function and inflammation , especially sCD40L , in early menopausal women , and the effect of common estrogen receptor ( ER ) polymorphisms on vascular responses to HT . STUDY DESIGN Eighty-four early menopausal women ( <3 years in menopause ) with menopausal complaints eligible for HT . Forty women received transdermal 17β-estradiol plus cyclical micronized progesterone for 3 months while 44 did not ( controls ) . MAIN OUTCOME MEASURES Brachial artery flow-mediated dilation ( FMD ) and vascular inflammation markers ( sICAM , sP-Selectin and sCD40L ) . Genetic polymorphisms of ERα ( PvuII 454 - 397T > C and XbaI 454 - 351A > G ) and ERβ ( AluI 1730A > G ) were also assessed . RESULTS The two groups did not differ at baseline . Following HT , vasomotor complaints ' severity , blood pressure , LDL , sCD40L , sICAM and sP-Selectin decreased and FMD increased compared to controls ( P<0.05 for all ) . ERβ AluI A allele presence was the most important independent predictor of  HT-induced increase in FMD while ERα XbaI A allele was the only independent predictor of decrease in sCD40L . CONCLUSIONS Short-term HT in early menopausal women improved endothelial function and inflammation . Specific ER polymorphisms that were found to be main determinants of HT-induced effects on endothelium could identify subgroups of women who may benefit the most from HT 
    Output:
    
ERβ seems to possess multiple functions in the female cardiovascular system .