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Sex differences in cardiomyocyte connexin43 expression.

Brian L Stauffer¹, Rebecca D Sobus, Carmen C Sucharov

¹Department of Medicine, Division of Cardiology, University of Colorado Denver, Aurora, CO 80045, USA. Brian.Stauffer@ucdenver.edu

Journal of Cardiovascular Pharmacology

|July 15, 2011

Summary

Female hearts show higher cardiac connexin43 (Cx43) expression, offering protection against arrhythmias. This sex difference, influenced by micro-RNA-1 (miR-1), enhances Cx43 function under pathological conditions.

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Area of Science:

Cardiovascular Science
Molecular Biology
Sex Differences in Physiology

Background:

Cardiac connexin43 (Cx43) is crucial for cell communication; reduced Cx43 is linked to arrhythmias.
Female hearts exhibit inherent resistance to arrhythmias, suggesting underlying protective mechanisms.

Purpose of the Study:

To investigate sex-based differences in Cx43 expression and regulation in cardiomyocytes.
To determine if Cx43 expression is higher in female cardiomyocytes under pathological stress.

Main Methods:

Isolated adult male and female rat ventricular myocytes.
Treatment with phenylephrine (PE) to induce pathological conditions.
Quantification of Cx43 mRNA, protein, and phosphorylation; measurement of micro-RNA-1 (miR-1) expression.

Main Results:

Female cardiomyocytes exhibited significantly higher Cx43 mRNA (1.4-fold) and protein (5-fold) levels than males, under basal and PE-treated conditions.
PE treatment increased Cx43 expression and phosphorylation only in female cardiomyocytes.
miR-1 expression was lower in PE-treated female cardiomyocytes, correlating with increased Cx43, while unchanged in males.

Conclusions:

A significant sex difference exists in Cx43 expression and phosphorylation, favoring cardioprotection in females.
Sex-specific regulation of miR-1 may underlie the observed differences in Cx43 expression under pathological stress.