Institute of Gender in Medicine

Berlin, Germany

Institute of Gender in Medicine

Berlin, Germany
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Foryst-Ludwig A.,Charité - Medical University of Berlin | Kreissl M.C.,University of Würzburg | Sprang C.,Charité - Medical University of Berlin | Thalke B.,Charité - Medical University of Berlin | And 13 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2011

Exercise-inducedcardiac hypertrophy has been recently identified to be regulated in asex-specific manner. In parallel, women exhibit enhanced exercisemediatedlipolysis compared with men, which might be linked tocardiac responses. The aim of the present study was to assess ifpreviously reported sex-dependent differences in the cardiac hypertrophicresponse during exercise are associated with differences incardiac energy substrate availability/utilization. Female and maleC57BL/6J mice were challenged with active treadmill running for 1.5h/day (0.25 m/s) over 4 wk. Mice underwent cardiac and metabolicphenotyping including echocardiography, small-animal PET, periexerciseindirect calorimetry, and analysis of adipose tissue (AT)lipolysis and cardiac gene expression. Female mice exhibited increasedcardiac hypertrophic responses to exercise compared withmale mice, measured by echocardiography [percent increase in leftventricular mass (LVM): female: 22.2 ± 0.8%, male: 9.0 ± 0.2%;P < 0.05]. This was associated with increased plasma free fatty acid(FFA) levels and augmented AT lipolysis in female mice aftertraining, whereas FFA levels from male mice decreased. The respiratoryquotient during exercise was significantly lower in female miceindicative for preferential utilization of fatty acids. In parallel, myocardialglucose uptake was reduced in female mice after exercise,analyzed by PET {injection dose (ID)/LVM [%ID/g]: 36.8 ± 3.5female sedentary vs. 28.3 ± 4.3 female training; P < 0.05}, whereascardiac glucose uptake was unaltered after exercise in male counterparts.Cardiac genes involved in fatty acid uptake/oxidation in femaleswere increased compared with male mice. Collectively, our datademonstrate that sex differences in exercise-induced cardiac hypertrophyare associated with changes in cardiac substrate availabilityand utilization. © 2011 the American Physiological Society.

Kararigas G.,Institute of Gender in Medicine | Kararigas G.,Charite University Hospital | Fliegner D.,Institute of Gender in Medicine | Fliegner D.,Charite University Hospital | And 4 more authors.
Physiological Genomics | Year: 2011

Cardiac hypertrophy, the adaptive response of the heart to overload, is a major risk factor for heart failure and sudden death. Estrogen (E2) and estrogen receptor beta (ERbeta) offer protection against hypertrophy and in the transition to heart failure. However, the underlying pathways remain incompletely defined. We employed a publicly available microarray dataset of female wild-type (WT) and ERbeta knockout (BERKO) mice subjected to pressure overload-induced hypertrophy to perform a systematic investigation of the mechanisms involved in the protection conferred by the E2/ERbeta axis. We show that considerably more genes were modulated in response to pressure overload in BERKO mice than in WT mice. The majority of the identified candidates in BERKO mice were induced, while those in WT mice were repressed. Pathway analysis revealed a similar pattern. This study is the first to demonstrate that the lack of ERbeta led to a significant increase of inflammatory pathways. Mitochondrial bioenergetics- and oxidative stress-related pathways were also modulated. In conclusion, ERbeta acquires the role of gatekeeper of the genomic response of the heart to pressure overload-induced hypertrophy. This may offer the molecular explanation for its cardioprotective role. We consider the present study to be a useful resource and that it will contribute to downstream functional analysis and to the characterization of pathways with previously unknown role in hypertrophy. © 2011 the American Physiological Society.

Fliegner D.,Institute of Gender in Medicine | Fliegner D.,Charité - Medical University of Berlin | Schubert C.,Institute of Gender in Medicine | Schubert C.,Charité - Medical University of Berlin | And 14 more authors.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology | Year: 2010

We investigated sex differences and the role of estrogen receptor-β (ERβ) on myocardial hypertrophy in a mouse model of pressure overload. We performed transverse aortic constriction (TAC) or sham surgery in male and female wild-type (WT) and ERβ knockout (ER-/-) mice. All mice were characterized by echocardiography and hemodynamic measurements and were killed 9 wk after surgery. Left ventricular (LV) samples were analyzed by microarray profiling, real-time RTPCR, and histology. After 9 wk, WT males showed more hypertrophy and heart failure signs than WT females. Notably, WT females developed a concentric form of hypertrophy, while males developed eccentric hypertrophy. ERβ deletion augmented the TAC-induced increase in cardiomyocyte diameter in both sexes. Gene expression profiling revealed that WT male hearts had a stronger induction of matrix-related genes and a stronger repression of mitochondrial genes than WT female hearts. ER-/- mice exhibited a different transcriptional response. ER-/-/TAC mice of both sexes exhibited induction of proapoptotic genes with a stronger expression in ER-/- males. Cardiac fibrosis was more pronounced in male WT/TAC than in female mice. This difference was abolished in ER-/- mice. The number of apoptotic nuclei was increased in both sexes of ER-/-/ TAC mice, most prominent in males. Female sex offers protection against ventricular chamber dilation in the TAC model. Both female sex and ERβ attenuate the development of fibrosis and apoptosis, thus slowing the progression to heart failure. Copyright © 2010 the American Physiological Society.

PubMed | Institute of Gender in Medicine
Type: Comparative Study | Journal: Cerebrovascular diseases (Basel, Switzerland) | Year: 2011

Major gender differences exist in cardiovascular diseases and lead to different outcomes in women and men. However, attention and incorporation of sex-/gender-specific research might vary among disciplines. We therefore conducted a systematic review comparing publication characteristics and trends between stroke and myocardial infarction (MI) with respect to sex- and gender-related aspects.A systematic literature search was performed in PubMed to identify gender-/sex-related articles published for stroke and MI between 1977 and 2008. A specifically designed text mining program was used, and all literature was rated by two independent investigators. Publications were classified according to type of research performed, publication year, funding, geographical location, and gender of first and last authors.962 articles were retrieved and limited to 405 (42%) gender-relevant publications; 131 on stroke and 274 on MI. Type of performed research differed, especially in disease management, which received little attention (17%) in stroke, while representing the major focus in MI (40%). In both areas, clinical presentation received little attention (3 and 5%). Although publications progressively increased in both fields, an 8- to 10-year time gap emerged for stroke compared to MI. Last authors in both areas were predominantly men, but female last authorship is increasing more significantly over time in the field of stroke. Research on sex and gender differences in MI and stroke is largely underfunded, particularly by the EU.The data demonstrate how sex-/gender-specific research differs between specialties, most likely due to the diverse interest, funding opportunities and authorship distributions identified.

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