Stress as a modifier of atherosclerosis - Novel mechanistic insights and therapeutic avenues -

Projektinformationen

STRATO

ID Finanzhilfevereinbarung: 759272

DOI

10.3030/759272

Projekt abgeschlossen

EK-Unterschriftsdatum 19 Dezember 2017

Startdatum 1 Februar 2018

Enddatum 31 Januar 2024

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 1 477 680,00

EU-Beitrag

€ 1 477 680,00

Koordiniert durch

DEUTSCHES HERZZENTRUM MUNCHEN
Germany

Periodic Reporting for period 4 - STRATO (Stress as a modifier of atherosclerosis - Novel mechanistic insights and therapeutic avenues -)

Berichtszeitraum: 2022-08-01 bis 2024-01-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Atherosclerosis is a chronic disease of the arterial vessel wall and a major cause of death in the EU and worldwide. The ultimate complication of atherosclerosis is the rupture of an atherosclerotic plaque with subsequent thrombosis causing a sudden partial or complete occlusion of the vessel. This results in emergencies, such as acute coronary syndrome (ACS, including myocardial infarction) and stroke. Plaque progression and destabilization, which humans experience as ACS, can be triggered by several conditions, among them mental stress (both acute and chronic). Yet, the effect of mental stress on plaque progression is poorly understood although a number of clinical and epidemiological studies linked social stressors to increased occurrence of cardiovascular diseases. Compared to chronic stress, acute mental stress is far more common and associated with an even greater incidence of cardiovascular events. In this project, our overall objective is to fill the gap in knowledge on how acute mental stress rapidly promotes plaque destabilization and to identify novel therapeutic measures to reduce acute mental stress related morbidity and mortality.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

Mental stress associates more strongly with the occurrence of myocardial infarction, a major contributor to worldwide mortality, than other classical risk factors, such as diabetes or hypertension. Despite this huge impact on public health, we do not yet fully understand the mechanisms nor does state-of-the-art treatment reduce stress-related risk.
Our study addresses this gap in mechanistic knowledge and reveals that after exposure to acute mental stress, norepinephrine acts on endothelial cells, leading to increased expression of adhesion molecules and augmented release of the chemokines CXCL1 and CCL7. As a consequence, monocyte and neutrophil recruitment occurs in susceptible tissues, particularly atherosclerotic plaques. We further provide evidence that these pre-clinical findings can be translated to humans with stress exposure and that specific therapeutic targeting of the stress response can beneficially alter the course of cardiovascular disease. In summary, our data provide new insights into how acute mental stress elevates vascular inflammation and promotes plaque rupture. We currently exploit our findings to develop novel strategies to relief stress and to build stress resilience. We disseminated our insights through our open-access publications and presentations at various international and national congresses.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

We finalized all planned experiments within the funding period. Our results provide an extensive, unequaled view on how acute mental stress aggravates atherosclerosis resulting in myocardial infarction and stroke. We gained ground-breaking insights and unraveled new disease mechanisms which provide the basis for future pharmaceutical treatment to reduce the burden of stress-induced mortality and morbidity.

overview of the main objectives

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