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Genomic upregulation of cardiac Cav1.2α and NCX1 by estrogen in women

Overview of attention for article published in Biology of Sex Differences, August 2017
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Title
Genomic upregulation of cardiac Cav1.2α and NCX1 by estrogen in women
Published in
Biology of Sex Differences, August 2017
DOI 10.1186/s13293-017-0148-4
Pubmed ID
Authors

Rita Papp, Glenna C. L. Bett, Agnieszka Lis, Randall L. Rasmusson, István Baczkó, András Varró, Guy Salama

Abstract

Women have a higher risk of lethal arrhythmias than men in long QT syndrome type 2 (LQTS2), but the mechanisms remain uncertain due to the limited availability of healthy control human tissue. We have previously reported that in female rabbits, estrogen increases arrhythmia risk in drug-induced LQTS2 by upregulating L-type Ca(2+) (ICa,L) and sodium-calcium exchange (INCX) currents at the base of the epicardium by a genomic mechanism. This study investigates if the effects of estrogen on rabbit ICa,L and INCX apply to human hearts. Postmortem human left ventricular tissue samples were probed with selective antibodies for regional heterogeneities of ion channel protein expression and compared to rabbit myocardium. Functionally, ICa,L and INCX were measured from female and male cardiomyocytes derived from human induced pluripotent stem cells (iPS-CMs) with the voltage-clamp technique from control and estrogen-treated iPS-CMs. In women (n = 12), Cav1.2α (primary subunit of the L-type calcium channel protein 1) and NCX1 (sodium-calcium exchange protein) levels were higher at the base than apex of the epicardium (40 ± 14 and 81 ± 30%, respectively, P < 0.05), but not in men (n = 6) or postmenopausal women (n = 6). Similarly, in cardiomyocytes derived from female human iPS-CMs, estrogen (1 nM, 1-2 days) increased ICa,L (31%, P < 0.05) and INCX (7.5-fold, - 90 mV, P < 0.01) and their mRNA levels (P < 0.05). Moreover, in male human iPS-CMs, estrogen failed to alter ICa,L and INCX. The results show that estrogen upregulates cardiac ICa,L and INCX in women through genomic mechanisms that account for sex differences in Ca(2+) handling and spatial heterogeneities of repolarization due to base-apex heterogeneities of Cav1.2α and NCX1. By analogy with rabbit studies, these effects account for human sex-difference in arrhythmia risk.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 32 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 28%
Student > Bachelor 5 16%
Researcher 5 16%
Student > Postgraduate 3 9%
Student > Master 3 9%
Other 3 9%
Unknown 4 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 25%
Agricultural and Biological Sciences 6 19%
Medicine and Dentistry 3 9%
Neuroscience 2 6%
Sports and Recreations 1 3%
Other 5 16%
Unknown 7 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 September 2017.
All research outputs
#9,026,133
of 11,753,826 outputs
Outputs from Biology of Sex Differences
#157
of 194 outputs
Outputs of similar age
#178,707
of 266,734 outputs
Outputs of similar age from Biology of Sex Differences
#5
of 5 outputs
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So far Altmetric has tracked 194 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.1. This one is in the 17th percentile – i.e., 17% of its peers scored the same or lower than it.
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