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1. The Institute of Gender in Medicine (GiM)
a. Research activities / projects
Evaluation of cardiovascular risk in women in Berlin (BEFRI study)
It is well known that women worldwide are inadequately informed about their risk for
cardiovascular disease and mortality. Risk factors differ between women and men and some
display a gender-specific distribution that is seldom accounted for in common risk scores.
Using the first women-specific risk score (the “Mosca-score”) as a reference for the
determination of objective cardiovascular risk, we will evaluate the ability of healthy women in
the general population to determine their specific cardiovascular risk profile. Reasons for
agreement and disagreement of the subjective and objective determinations will be identified
and used for the ultimate goal to improve preventive offers for women.
Project Coordination: Mirjam Rücke, MA; Sabine Oertelt-Prigione, MD MScPH,
Ute Seeland, MD; Vera Regitz-Zagrosek, MD, Professor of Cardiology
eGender Medicine – Education for many professionals as possible!
The Institute of Gender in Medicine (GIM) in Germany develops a professional eLearning
course on gender medicine, educating as many students and professionals all over the
world. The aim is to qualify physicians to understand the goals, principles and knowledge of
gender medicine and integrating gender-sensitive aspects into medical practice. This project
is based on a well-tested curriculum for higher education established by internationally
renowned experts on Gender Medicine. Gender facts will be communicated with the help of
diverse “learning tools” integrating interactive elements for more motivation and learning
success. Knowledge is based on > 10.000 articles collected in the GenderMed database.
“Go Live!” for the eLearning course “eGender Medicine” will be January 2014.
Project coordination: Ute Seeland, MD, Vera Regitz-Zagrosek, MD, Professor of Cardiology
German Center for Cardiovascular Research (GCCR)
„Vera Regitz-Zagrosek is coordinator of “Cardio-Berlin”, the Berlin representation in the
novel “German Centre for Cardiovascular Research”(GCCR), where the partners bundled
their research in the fields of the cardiovascular and metabolic systems. Berlin is with Charité
– Universitätsmedizin Berlin, Max-Delbrück-Center for Molecular Medicine (MDC) and the
German Heart Institute (DHZB) one of seven locations of the GCCR. Goal of the GCCR is
the direct translation of basic research results to praxis by close cooperation with the clinics.
„Cardio-Berlin“ focuses on prevention and additionally on sex differences in cardiovascular
diseases. Clinicians and researchers work together interdisciplinarily and deal with the latest
methods in molecular genetics and imaging techniques as well as approaches of systems
biology.
Women suffering from heart failure (HF) have a better prognosis than men. Furthermore, the
relevance of risk factors and the therapeutic response differ between women and men.
Based on own previous results and external as well, the scientists of the GiM hypothesize
that 17β-estradiol and/or its receptors regulate cardiac Ca2+ metabolism and contractility in a
sex-specific manner and lead to sex differences within the cardiovascular system. We want
to clarify underlying mechanisms to develop new therapeutic target structures.
Project Coordination: Vera Regitz-Zagrosek, MD, Professor of Cardiology
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Research Group Myocardial Hypertrophy (FOR 1054)
Prof. Vera Regitz-Zagrosek is coordinator of the DFG research group
„Myokardhypertrophie“ (FOR 1054). The research group assembles 8 working groups of
excellent scientists of Charité-Universitätsmedizin Berlin, the German Heart Institute Berlin
(DHZB) and Max-Delbrück-Center for Molecular Medicine (MDC) and achieved successfully
the second funding period.
The main goal of that research group is the analysis of gender differences in the adaptation
of the heart to mechanical stress. We perform a series of mechanical analysis using cell
cultures and animal models. This includes models of physiological and pathological
myocardial stress, e.g. strength training and hypertension.
The role of sexual hormones and their receptors selectively analysed. Moreover, the effect of
sex hormones on the lipid turnover is investigated.
The working group of Prof. Vera Regitz-Zagrosek at the GiM collaborates with clinical
projects and focuses here especially on gender differences in myocardial reaction to
overload due to aortic valve disease.Based on our previous findings, we hypothesize that
estrogen (E2) and its receptors ERα and ERβ modify the cardiac response to mechanical
load by regulating mitochondrial function and energy metabolism. AKT signaling and key
regulators of mitochondrial function and metabolic genes are probably involved in these
processes. We will investigate sex differences in mouse models of physiological and
pathological MH. This involves the analysis of sex-specific regulation of genes encoding
proteins involved in energy metabolism, micro-RNAs and protein patterns. Further, we
analyse the mechanisms leading to the sex differences in the cardiac phenotypes. In cell
culture experiments we will dissect the effects of E2-activated ERα and ERβ on key factors
that control mitochondrial gene expression, such as MEF2, PGC-1α and PPARs and we will
determine their expression level and/or transcriptional activity after selective gene silencing
of ERs. The project will identify sex-specific MH mechanisms with therapeutic potential
relevant to both genders.
Project Coordination: Vera Regitz-Zagrosek, MD, Professor of Cardiology
Graduate Course 754
Prof. Vera Regitz-Zagrosek, director of GiM, coordinated the graduate course „Sex
specific mechanisms in myocardial hypertrophy“ (GK754) funded by the German
Research Foundation from 2004 to 2011 very successful. Within that common research
project 12 working groups of Charité-Universitätsmedizin Berlin cooperated, among them 8
of Center for Cardiovascular Research CCR and German Heart Institute Berlin. It comprised
four interconnected modules:
 Animal models of hypertrophy,
 functional genomics and proteomics,
 gender-specific molecular mechanisms and
 gender aspects in the clinics of cardiovascular diseases
 Whithin 3 funding periods more than 40 cand. med. and cand. vet. med. applicants as
well 19 PhD students could finish their thesis until now. Eleven PhD students will
finish in 2012.
 The GK754 is sustained in the activities of the initiative “Young CCR”. A novel
international activity is planned as follow up.
Project Coordination: Vera Regitz-Zagrosek, MD, Professor of Cardiology
Gender differences in human aortic stenosis
The GiM designed a single project to link basic and clinical research in analysing gender
differences in human aortic stenosis in 2006. The project was funded by the DFG, German
Research Foundation (DFG-Re 662/6-1, Dwo 70/1-1). Prof. Vera Regitz-Zagrosek together
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with the young scientist Dr. Elke Dworatzek, who finished their PhD thesis at the GiM, now
re-applied for the prolongation.
Women with aortic stenosis (AS) develop, under similar pressure load conditions, a more
concentric form of left ventricular hypertrophy (LVH) with better preserved systolic function,
compared to men. We found in intra-operative biopsies from AS patients, that men showed a
stronger induction of pro-fibrotic gene expression compared to women. Woman exhibit
postoperatively a faster LVH regression. After transverse aortic constriction (TAC), male
mice develop more cardiac fibrosis. 17β-Estradiol (E2) regulates collagen I and III differently
in isolated cardiac fibroblasts from male and female rats.
Goal of this project is to show, that the sex-specific regulation of cardiac fibrosis leads to sex
differences in the development of LVH and regression with clinical relevance. Therefore, we
will analyze underlying mechanisms leading to sex differences in LVH in the human heart
and link them to the clinical course and LVH regression. In a mice model with pressure
overload (TAC) and unloading, we want to dissect underlying molecular mechanisms.
Previous findings indicate a role of E2 and estrogen receptors (ER). We will therefore
determine if ER transcriptional activity is differently modulated in cardiac fibroblasts of both
sexes and which other mechanisms may be involved. These data will enhance our
understanding of LVH and fibrosis, and enable sex-specific therapeutic approaches.
Project Coordination: Vera Regitz-Zagrosek, MD, Professor of Cardiology
EUGeneHeart - European Integrated Project (018833)
Prof. Regitz-Zagrosek coordinated task 4 “gender” of in the EU-funded EUGeneHeart
project. The project aimed at the elucidation of the mechanisms leading from myocardial
hypertrophy to heart failure and included collaboration with research groups at the INSERM
(Institut National de la Santé et de la Recherche Médicale) and the Karolinska Institute. Aim
was the investigation of gender differences in myocardial hypertrophy induced by stress,
training, infarction and pressure. Experiments were performed using cell cultures and animal
models and focused on the role of sex hormones.
Even if fundig is completed, the fruitful cooperations persist. Running analyses deal with sex
differences in remodeling processes of the extracellular matrix after myocardial infarction.
Publication of the results is in progress.
Project Coordination: Vera Regitz-Zagrosek, MD, Professor of Cardiology
Gender Research at Center for Cardiovascular Research (CCR)
PI: Prof. Dr. Vera Regitz-Zagrosek
Co-PIs: Prof. Stefan Anker, Prof. Dr. Duska Dragun, Prof. Dr. Ulrich Kintscher, Prof. Dr.
Franz Theuring, Prof. Dr. Carsten Tschöpe, Prof. Dr. Thomas Unger, .... open for other
collaborations.
Cooperation: Institute of Gender in Medicine (GiM)
Aim of this project at the
Center for Cardiovascular Research (CCR) is the investigation
of gender differences in cardiologic and renal diseases and the definition of the role of sex
hormones. All research groups already collaborated in the graduate course “GK 754 “Gender
specific mechanisms of myocardial hypertrophy”. Furthermore, three projects analyzing sex
differences were part of the EST-Program “Cardiovasc”, which focuses on the effects of
estrogen on the myocardial tissue and the role of the newly identified estrogen receptor
GPR-30.
In the context of further research activity, we established three mouse models with known
sex differences at the CCR: one model for pressure induced hypertrophy (transverse aortic
constriction), one model for salt-induced hypertrophy (DOCA-salt) and a model for
physiological hypertrophy after spontaneous physical activity. In these models we will
investigate differences in cardiomyocyte signalling due to sex differences and
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estrogen/androgen driven differences. Furthermore, we are investigating the influence of sex
hormones on gene expression and the proteome in a systematic manner.
b. Teaching activities:
i.
Workshops, meetings
ii. Courses
Elective Course "Gender-related Medicine"
Women and men display relevant differences in pathogenesis and clinical features and
prognosis of diseases. Moreover, diagnostic and therapeutic options are not necessarily
identical. There is still a gap between gender research and incorporation of the results into
clinical practice.
The elective course "Gender-related medicine" has been designed to fill this gap and to
systematically integrate gender-specific approaches into medical education. The course is
designed as a series of interdisciplinary lectures, with two additional seminar dates where
course participants will present their elaborations on a chosen topic.
Much attention will be paid to integration of clinical and research practice. In fact, most
specialties will include a series of case presentations. The elective course represents a
significant addition to the regular medical curriculum in conveying the systematic analysis of
sex and gender in disease pathogenesis and evolution.
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