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JCI online ahead of print table of contents for May 16, 2014
Date:5/16/2014

="_blank" href="http://www.jci.org/articles/view/75090">http://www.jci.org/articles/view/75090

ACCOMPANYING COMMENTARY TITLE: Unraveling the relationship between microbial translocation and systemic immune activation in HIV infection

AUTHOR CONTACT: Robert F. Siliciano
Johns Hopkins Univ Schl Of Medicine, Baltimore, MD, USA
Phone: 410/955-2958; Fax: 410-955-0964; E-mail: rsiliciano@jhmi.edu

View this article at: http://www.jci.org/articles/view/75799


Estrogen underlies sex-specific responses to sildenafil

Heart disease is the leading cause of death in both men and women; however, the disease has a somewhat different clinical presentation in women that has been attributed to estrogen levels. Interestingly, estrogen may underlie sex-specific differences in the efficacy of treatments for heart disease. In the issue of the Journal of Clinical Investigation, Eiki Takimoto and colleagues at Johns Hopkins University School of Medicine investigated the impact of estrogen on the cardioprotective effects of sildenafil, a cGMP-specific phosphodiesterase 5 (PDE5) inhibitor. PDE5 inhibitors block hydrolysis of cGMP, leading to activation of the cGMP-dependent kinase Iα (PKGIα), which prevent pathogenic remodeling of the heart. Using two different murine models of heart disease, Takimoto and colleagues determined that sildenafil ameliorates cardiac pathology in an estrogen-dependent manner in female mice. In female hearts, estrogen maintained constitutive activation of eNOS, leading to tonic synthesis of cGMP; in contrast, male hearts exhibited stress-induced eNOS activation and cGMP synthesis, making sildenafil's effects independent of estrogen. In the accompanying commentary, Elizabeth Murphy and Charles Steenbergen discuss how sex-dependent
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Contact: Corinne Williams
press_releases@the-jci.org
Journal of Clinical Investigation
Source:Eurekalert

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