Abstract
Using genetically engineered mice lacking estrogen receptor-α non-nuclear signaling, this study demonstrated that estrogen receptor−α non-nuclear signaling activated myocardial cyclic guanosine monophosphate-dependent protein kinase G and conferred protection against cardiac remodeling induced by pressure overload. This pathway was indispensable to the therapeutic efficacy of cyclic guanosine monophosphate−phosphodiesterase 5 inhibition but not to that of soluble guanylate cyclase stimulation. These results might partially explain the equivocal results of phosphodiesterase 5 inhibitor efficacy and also provide the molecular basis for the advantage of using a soluble guanylate cyclase simulator as a new therapeutic option in post-menopausal women. This study also highlighted the need for female-specific therapeutic strategies for heart failure.
Original language | English |
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Pages (from-to) | 282-295 |
Number of pages | 14 |
Journal | JACC: Basic to Translational Science |
Volume | 5 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2020 |
Externally published | Yes |
Keywords
- cyclic GMP
- estradiol
- heart failure
- non-nuclear signaling
- sGC stimulator