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Gender-Differences in Heart-Brain-Crosstalk: Role of Inflammation, Sympathetic Pathways, and Psychosocial Complexity

English title Gender-Differences in Heart-Brain-Crosstalk: Role of Inflammation, Sympathetic Pathways, and Psychosocial Complexity
Applicant Gebhard Catherine
Number 190074
Funding scheme SNSF Professorships
Research institution University of Zurich Institute for Pharmacology & Toxicology Nuclear Medicine
Institution of higher education University of Zurich - ZH
Main discipline Cardiovascular Research
Start/End 01.06.2020 - 31.05.2022
Approved amount 800'000.00
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Keywords (8)

Gender; Positron emission tomography-computed tomography; Cardiovascular magnetic resonance imaging ; Ischemic heart disease; Cardiovascular disease; Cardiac imaging; Stress response; Heart-Brain interaction

Lay Summary (German)

Lead
In Europa sterben derzeit mehr Frauen als Männer an Herz-Kreislauferkrankungen. Alarmierend ist zudem ein Anstieg der koronaren Herzerkrankung bei jüngeren Frauen. Trotz dieser Tendenzen ist derzeit unzureichend erforscht, welche Besonderheiten das weibliche Herz aufweist und welche Faktoren für dessen erhöhte Vulnerabilität verantwortlich sind.
Lay summary

Inhalt und Ziele des Forschungsprojektes

Unsere Forschungsgruppe konnte mittels neuester bildgebender Verfahren zeigen, dass die  Amygdala - das sogenannte Angstzentrum des Gehirns- bei Frauen mit Durchblutungsstörungen des Herzens hochaktiv ist, während dies bei herzkranken Männern nicht der Fall ist. Erstmals konnte somit ein neurobiologischer Mechanismus gefunden werden, der aufzeigt, dass sich Frauen mit Herzerkrankungen in einer Art Dauerstress und chronischem Angstzustand befinden. Unsere Beobachtungen implizieren, dass gezielte Maßnahmen zur Stressreduktion bei Frauen mit Herzerkrankungen eine zentrale Rolle bei der Behandlung spielen sollten. In unserem Forschungsprojekt untersuchen wir nun Steuerungsmechanismen auf molekularer und zellulärer Ebene, die für die erhöhte Stressreaktion der herzkranken Frauen verantwortlich sind. Hierzu ist eine interdisziplinäre Studie geplant, die mittels neuester Technologien die Kommunikation von Gehirn und Herz untersucht. Eine sogenannte Hybridbildgebung ermöglicht es, zeitgleich molekulare Mechanismen mittels Positronen-Emissions Tomographie darzustellen als auch anatomische und funktionelle Daten von Gehirn und Herz durch Magnetresonanztomographie zu gewinnen.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojektes

Die Ergebnisse unserer Studie sollen die Entwicklung spezifischer und wirkungsvoller kardiovaskulärer Behandlungsmethoden in der zunehmend gefährdeten Population der herzkranken Frauen ermöglichen.

Direct link to Lay Summary Last update: 01.05.2020

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
163892 Age-dependent Remodelling of the Female Heart - Protective or Detrimental? 01.06.2016 SNSF Professorships

Abstract

Background: Cardiovascular deaths in women currently exceed those in men. Most intriguingly, recent U.S. and European studies report a significant increase in the incidence and case-fatality of ischemic heart disease (IHD) in young women <55 years. Despite these alarming tendencies, evidence to date has failed to adequately explore unique female determinants of cardiovascular disease (CVD). This is mainly due to the limited test accuracy of contemporary cardiovascular diagnostic approaches in women as well as a substantial underrepresentation of women in cardiovascular studies, with women accounting for <20% of the study population. Given the lack of data on female determinants of cardiovascular risk, we hypothesize that in currently used diagnostic and therapeutic approaches critical variables responsible for the problematic trends seen in women are still unknown. Amongst those are non-traditional risk conditions specific to women alone, such as genetics, female-specific biological variables, gender-specific lifestyle as well as psychosocial factors. Indeed, there is evidence that an overstimulation of the sympathetic nervous system and structures associated with the limbic network make women more vulnerable to the adverse associations of mental stress and cardiovascular health. The latter is an intriguing concept given that psychosocial stress has substantially increased for women during the last two decades due to a continuous increase in women’s economic participation and educational attainment.Aims and methods: Thus, this project intends to identify female-specific targets for CVD prevention and treatment. Our aims will be to (1) characterise the role of neuroimmune communication systems, sex hormones, and adrenergic activity in neuronal stress responses to myocardial injury in a murine model of myocardial infarction, and (2) to elucidate the impact of gender-specific psychosocial components on heart-brain crosstalk in postmenopausal women and aged men free of CVD. The relative contribution of sex steroids, inflammation, and neurohumoral factors to myocardial perfusion abnormalities and metabolic activity in key neuronal structures involved in stress responses will be evaluated in vivo by serial multi-system imaging in mice. In a complementary clinical study, the impact of psychosocial variables and non-traditional risk factors on stress-based neuro-cardiac circuitries will be assessed in sixty women and men free of CVD.Relevance and Impact: As the mechanisms contributing to the excess risk in women remain largely unclear, llandmark gender-specific research identifying novel targets reflecting women’s biological systems and behavior is urgently needed. As such, the brain’s stress network and its downstream consequences is a promising signaling pathway given the predisposition of women to mental stress-induced ischemia and sympathetic over-activity. Indeed, designing therapies and interventions that can interrupt a vicious cycle between stress and cardiovascular events is an attractive strategy to target cardiovascular health inequalities between women and men linked to modifiable risk factors. Further, the planned project may help to overcome the limitations of contemporary diagnostic and therapeutic tools in women and lay the basis for future clinical intervention trials targeting behavioral upstream portions of the heart-brain axis as well as its downstream effectors.
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