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Volume 1 Issue 9, September 2022

The ‘sunset years’ come with sex differences in cardiometabolic health

Using a large cohort of people that spans three generations, Zhernakova et al. find that sex differences in risk factors and biomarkers for cardiometabolic diseases change dynamically with age.

See Zhernakova et al. and News & Views by Miller and Heather

Image: Jingyuan Fu, University Medical Center Groningen. Cover Design: Bethany Vukomanovic

Research Highlights

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News & Views

  • Changes in gene regulatory networks leading to species-specific variations in cardiac structure and function remain to be fully investigated. A new study presents a repertoire of human-gained (absent in mice) cis-regulatory elements, some of which appear to be involved in the acquisition of human-specific cardiac features.

    • Mirana Ramialison
    News & Views
  • Sex–age disparities in disease risk have been a neglected topic in cardiometabolic disease research. Zhernakova et al. demonstrate that risk factors and metabolic predictors covary with both sex and age: that is, men and women are different, and these differences are not static but change with age.

    • Jack J. Miller
    • Lisa C. Heather
    News & Views
  • Recent developments in high-throughput, in-depth sequencing platforms are providing opportunities to improve our understanding of biology and disease. Here, Kuppe et al. use a combinatorial approach to relate transcriptional changes to translational and functional implications for the heart in response to myocardial infarction.

    • Martijn Wehrens
    • Louk T. Timmer
    • Eva van Rooij
    News & Views
  • A landscape view of metabolic remodeling in end-stage human failing hearts generated by multiomics analysis confirms main changes in cardiac energy metabolism and challenges several widely held mechanisms derived from animal models. Further validation in non-end-stage heart failure and metabolic flux analysis will be necessary to move the field forward.

    • Akira Yoshii
    • Rong Tian
    News & Views
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Research Briefings

  • Heart failure is marked by metabolic insufficiency, but detailed understanding of the underlying metabolic rewiring has been limited. By applying state-of-the-art mass spectrometry to a large pool of human hearts in end-stage heart failure, we unveil numerous metabolic aberrations in human heart failure.

    Research Briefing
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  • In this Review, the authors provide an overview of the critical studies reporting Cre and CreER toxicity in the cardiovascular system, discuss the mechanisms proposed to underlie Cre toxicity and highlight the need to understand, eliminate and control for Cre/CreER toxicity in each experimental model.

    • Victoria S. Rashbrook
    • James T. Brash
    • Christiana Ruhrberg
    Review Article
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  • Destici, Zhu, et al. identify human-specific cis-regulatory elements (CREs) through a comparative epigenomic analysis of human and mouse cardiomyocytes at early stage of development and show that these CREs could contribute to species-specific cardiac features. Human-specific enhancers were particularly enriched in SNPs associated with human-specific traits (such as increased heart resting rate, atrial fibrillation and QRS duration), and the acquisition of human-specific enhancers could expand the functionality of the conserved transcriptional regulator ZIC3 by modifying its spatio-temporal expression.

    • Eugin Destici
    • Fugui Zhu
    • Neil C. Chi
  • With the use of the Lifelines cohort, Zhernakova and colleagues set out to characterize sex differences in cardiometabolic risk factors, metabolites and proteins in adults aged 20–80 years and find a strong age effect on sex differences in cardiometabolic disease risk factors and biomarkers.

    • Daria V. Zhernakova
    • Trishla Sinha
    • Jingyuan Fu
    Article Open Access
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