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April 24, 2026Journal of the American College of CardiologyOpen Access

Transcriptome Characterization of Estrogen-Treated Human Myocardium Identifies Myosin Regulatory Light Chain Interacting Protein as a Sex-Specific Element Influencing Contractile Function

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Key result

17β-estradiol induced MYLIP expression in male cardiac tissues only, leading to impaired contractile function and augmented myosin regulatory light chain ubiquitination in male cardiomyocytes.

Why the study?

Does 17β-estradiol (E2) treatment affect gene regulation and contractile function in a sex-specific manner in human and mouse cardiomyocytes?

Population

Human cardiac tissues from men and women, and isolated cardiomyocytes from hearts of male and female mice

Comparison

17β-estradiol (E2) treatment vs Untreated/control (implied)

Design

Preclinical

Authors

GKGeorgios KararigasGeneral CardiologyVBVirginie BitoHasselt UniversityHTHanna TinelBayer (Germany)

Discussion

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Implication

Warrants caution with elevated E2 in males; leaves open MYLIP modulation as sex-specific target to preserve contractility.

Key Points

  • This research aims to determine how the hormone 17β-estradiol (E2) affects gene regulation in human cardiac tissue and its role in contractile function across sexes.
  • Performed genome-wide expression profiling of E2-treated cardiac tissues from both men and women.
  • Studied gene expression and contractile function in cardiomyocytes from E2-treated male and female mice.
  • Utilized isolated mouse cardiomyocytes to confirm E2's sex-specific effects on contractile function.
  • Identified 36 E2-dependent genes regulated in a sex-specific manner; MYLIP was specifically induced in men.
  • E2 treatment led to impaired contractile function in male cardiomyocytes, with increased Mylip mRNA and protein levels.
  • Demonstrated that cardiac myosin regulatory light chain is a substrate for MYLIP, resulting in increased ubiquitination.

Structured PICO

Does 17β-estradiol (E2) treatment affect gene regulation and contractile function in a sex-specific manner in human and mouse cardiomyocytes?

P
Population
Human cardiac tissues from men and women, and isolated cardiomyocytes from hearts of male and female mice
I
Intervention
17β-estradiol (E2) treatment
C
Comparator
Untreated/control (implied)
O
Outcome
Gene expression profiling (specifically MYLIP induction) and contractile function in cardiomyocytessurrogate

17β-estradiol induces MYLIP expression and impairs contractile function specifically in male cardiomyocytes, suggesting a sex-specific mechanism that could influence cardiovascular disease risk in men with elevated E2.

Cite This Study

Kararigas et al. (2012) studied Cardiovascular disease. 17β-estradiol (E2) was evaluated on Gene regulation and contractile function. 17β-estradiol induced MYLIP expression in male cardiac tissues only, leading to impaired contractile function and augmented myosin regulatory light chain ubiquitination in male cardiomyocytes.

synapsesocial.com/papers/69eb89de39a85df2738599fchttps://doi.org/10.1016/j.jacc.2011.09.054
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