The function of B cells in myocardial infarction-accelerated atherosclerosis

Informazioni relative al progetto

The B-MIracle

ID dell’accordo di sovvenzione: 101041206

DOI

10.3030/101041206

Data della firma CE 8 Settembre 2022

Data di avvio 1 Gennaio 2023

Data di completamento 31 Dicembre 2027

Finanziato da

• European Research Council (ERC)

Costo totale

€ 1 475 638,75

Contributo UE

€ 1 475 638,75

Coordinato da

MEDIZINISCHE UNIVERSITAET WIEN
Austria

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

Periodo di rendicontazione: 2023-01-01 al 2025-06-30

Sintesi del contesto e degli obiettivi generali del progetto

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.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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?