Eastern Kentucky University

Poster Title

Estrogen Mediated Regulation of TGF-β Pathway Signaling in Cardiac Hypertrophy

Institution

Eastern Kentucky University

Abstract

It is well documented that pre-menopausal women are protected from heart disease, in part through the effects of estrogen. The cellular mechanisms activated by estrogen are interesting due to undesirable side effects linked to estrogen therapy in practice. Once understood, these mechanisms can be targeted for cardioprotective therapeutic approaches. We focused on the TGFβ pathway, known to promote cardiac hypertrophy. Estrogen treatment can prevent the development of hypertrophy in cardiomyocytes and estrogen treatment attenuates TGFβ signaling in cardiomyocyte hypertrophy. However, the relationship between the two is unclear. Our working hypothesis is that estrogen mediates its cardioprotective effects through activating microRNAs (miRNA), which in turn target TGFβ member transcripts, inhibiting TGFβ signaling. The miRNAs are a class of functional RNAs inhibiting the expression of gene targets. To address the control of the TGFβ family expression by estrogen; we performed a series of in vivo experiments comparing levels of TGFβ family members and targeting miRNAs in male and female mice who had undergone a surgical procedure inducing cardiac hypertrophy, as well as sham surgical mice and those of various ages without surgical intervention. Next Generation Sequencing was performed to establish miRNA profiles in male and female cardiac hypertrophy. Using Target Scan, we determined which differentially expressed miRNAs likely inhibit TGFβ family members. We confirmed sex differential expression of TGFβ family members and potential inhibitory miRNA using TaqMan assays. Our identified miRNAs can be used as targets for the development of new therapies to bypass estrogen’s negative effects.

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Estrogen Mediated Regulation of TGF-β Pathway Signaling in Cardiac Hypertrophy

It is well documented that pre-menopausal women are protected from heart disease, in part through the effects of estrogen. The cellular mechanisms activated by estrogen are interesting due to undesirable side effects linked to estrogen therapy in practice. Once understood, these mechanisms can be targeted for cardioprotective therapeutic approaches. We focused on the TGFβ pathway, known to promote cardiac hypertrophy. Estrogen treatment can prevent the development of hypertrophy in cardiomyocytes and estrogen treatment attenuates TGFβ signaling in cardiomyocyte hypertrophy. However, the relationship between the two is unclear. Our working hypothesis is that estrogen mediates its cardioprotective effects through activating microRNAs (miRNA), which in turn target TGFβ member transcripts, inhibiting TGFβ signaling. The miRNAs are a class of functional RNAs inhibiting the expression of gene targets. To address the control of the TGFβ family expression by estrogen; we performed a series of in vivo experiments comparing levels of TGFβ family members and targeting miRNAs in male and female mice who had undergone a surgical procedure inducing cardiac hypertrophy, as well as sham surgical mice and those of various ages without surgical intervention. Next Generation Sequencing was performed to establish miRNA profiles in male and female cardiac hypertrophy. Using Target Scan, we determined which differentially expressed miRNAs likely inhibit TGFβ family members. We confirmed sex differential expression of TGFβ family members and potential inhibitory miRNA using TaqMan assays. Our identified miRNAs can be used as targets for the development of new therapies to bypass estrogen’s negative effects.