The function of B cells in myocardial infarction-accelerated atherosclerosis

Projektinformationen

The B-MIracle

ID Finanzhilfevereinbarung: 101041206

DOI

10.3030/101041206

EK-Unterschriftsdatum 8 September 2022

Startdatum 1 Januar 2023

Enddatum 31 Dezember 2027

Finanziert unter

• European Research Council (ERC)

Gesamtkosten

€ 1 475 638,75

EU-Beitrag

€ 1 475 638,75

Koordiniert durch

MEDIZINISCHE UNIVERSITAET WIEN
Austria

Periodic Reporting for period 1 - The B-MIracle (The function of B cells in myocardial infarction-accelerated atherosclerosis)

Berichtszeitraum: 2023-01-01 bis 2025-06-30

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Heart attacks are the main cause of death worldwide. The main underlying pathology of this severe clinical manifestation is atherosclerosis, a lipid-driven chronic inflammatory disease that leads to the formation of atherosclerotic plaques in arteries. Rupture or erosion of atherosclerotic lesions in a coronary artery can trigger the formation of a thrombus and thereby restrict the blood flow in the heart muscle and ultimately cause myocardial infarction (MI). B lymphocytes, which are immune cells that produce antibodies and protect from microbial threats, play a major role in atherosclerosis and post-MI cardiac injury. Importantly, MI can accelerate the formation or preexisting atherosclerotic plaques and thus, increase the risk of recurrent MI. The mechanism by which MI accelerates atherosclerosis require further investigation. “The B-MIracle” project aims to investigate how B lymphocytes are implicated in the acceleration of atherosclerosis upon MI. To investigate this, we study genetically modified mice with atherosclerosis and MI, and investigate tissue specimens from patients with cardiovascular disease. These studies could enable the identification of novel mechanisms by which the immune system promotes the progression of atherosclerosis after a heart attack and consequently enable the development of precise therapeutic strategies for the secondary prevention of cardiovascular disease.

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

To investigate the functions of B cells in post-MI accelerated atherosclerosis, we study atherosclerosis-prone genetically modified mice that lack or overexpress genes involved in key signaling pathways for the activation of B cells. In addition, we test the effect of drugs, which are already approved and used in the clinic, in mouse models of accelerated atherosclerosis after MI. Furthermore, we investigate the changes in B cells, with respect to gene expression and antibody production, in humans after a heart attack.

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 found that B cells respond to MI in atherosclerosis-prone mice by altering their gene expression profile. Next, we will investigate the functions of candidate genes in driving the effects of B cells in MI-accelerated atherosclerosis. These studies could reveal signaling pathways that could be targeted therapeutically to mitigate the deleterious effect of MI in accelerating established atherosclerosis.

How do B cells affect MI-accelerated atherosclerosis?