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Estrogen Receptor-? Non-Nuclear Signaling Confers Cardioprotection and Is Essential to cGMP-PDE5 Inhibition Efficacy.

ABSTRACT: Using genetically engineered mice lacking estrogen receptor-? non-nuclear signaling, this study demonstrated that estrogen receptor-? 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.

SUBMITTER: Fukuma N 

PROVIDER: S-EPMC7091505 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Estrogen Receptor-α Non-Nuclear Signaling Confers Cardioprotection and Is Essential to cGMP-PDE5 Inhibition Efficacy.

Fukuma Nobuaki N   Takimoto Eiki E   Ueda Kazutaka K   Liu Pangyen P   Tajima Miyu M   Otsu Yu Y   Kariya Taro T   Harada Mutsuo M   Toko Haruhiro H   Koga Kaori K   Blanton Robert M RM   Karas Richard H RH   Komuro Issei I  

JACC. Basic to translational science 20200304 3

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. T  ...[more]

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