Investigation of the molecular mechanisms and consequences of the immune imbalance in coronary artery disease

Coronary artery disease (CAD) and its primary complication, myocardial infarction, remain a leading cause of death and disability.

Despite extensive treatment, residual inflammatory risk for recurrent cardiovascular events is high in CAD patients, and remains a diagnostic and therapeutic challenge.

Our previous findings suggest that immune imbalance in CAD, associated with aging and deficits of NK cells and regulatory T cells, is linked to inflammation and oxidative stress. Still, molecular mechanisms and consequences of immune imbalance in CAD are mainly unknown.

Based on our preliminary data, we hypothesize that immunoregulatory functions are impaired in CAD, but can be improved and even restored.

Accordingly, the overarching purpose of this project is to delineate the drivers and potential consequences of immune imbalance and explore the possibility for its restoration.To achieve this, we will a) further characterize the immunoregulatory dysfunction in CAD by using in vivo and ex vivo stress models and thereby explore strategies to restore it; b) study the impact of thymic involution on immune imbalance and CAD; c) develop clinical tools to identify patients with dysregulated inflammation; and d) investigate the effects of a novel vaccine strategy against influenza in CAD patients that addresses their immune imbalance.The proposed project has the potential to generate novel and creative insights into the diagnosis and management of residual inflammatory risk in CAD.