Ongoing Projects

Berenice Martinez: Long-Term Consequences of COVID-19 in Cardiovascular disease

COVID-19 is triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and, in addition to acute respiratory disorders, it is characterized by hyper inflammation and intravascular complications, such as thrombotic events. The long-term effects of the disease are poorly known, and our main aim is to resemble COVID-19 in an animal model of cardiovascular disease to unravel its long-term effects. To better appreciate the links between cardiovascular disease (CVD) and COVID-19, it is important to understand the underlying pathobiology of SARS-CoV-2 infection in vascular cells. Transgenic mouse models, enabling us to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediated long-term consequences on vascular and cardiac dysfunction fostering CVD. The project holds the promise of providing insight into yet unknown downstream signalling events triggered by SARS-CoV-2 and involved in the observed vasculopathies.

Bryce Evans: Unravelling the role of vascular ChemR23 expression in atherosclerosis

Chemokine receptors are important in perpetuating chronic vascular inflammation. Our published work (Van der Vorst et al., ATVB 2019) showed that hematopoietic deficiency of the chemokine like receptor ChemR23 increases the proportion of alternatively activated M2 macrophages and attenuated pDC recruitment to lymphatic organs and atherosclerotic lesions, in murine models. This synergistically restricts atherosclerotic lesion progression. However, conflicting results in systemic ChemR23-deficient animals (Laguna-Fernandez et al., Circulation 2018) suggesting ChemR23 has a diverse role within atherosclerosis. Therefore, we will investigate the role of ChemR23 on arterial endothelial and smooth muscle cells. Our data proposes that somatic -most likely vascular- ChemR23 expression has an atheroprotective role in atherosclerosis and may even orchestrate an anti-inflammatory response in vascular endothelial and smooth muscle cells.

Manovriti Thakur: Exploring NET-driven arterial thrombosis in LEAD and LEAD-specific intimal and medial calcification.

Even though atherosclerosis is widely studied in other arterial beds, knowledge on LEAD is very limited. Neutrophil extracellular traps (NETs) are known to accelerate plaque rupture induced atherothrombosis. NETs scaffold act as a podium for red blood cells, platelets, fibrinogen, platelet microvesicles and coagulation factor binding. However, the details of these interactions in the LEAD-specific atherothrombosis are still missing. Consequently, our first aim is to analyze the role of NET scaffold and its interaction with coagulation factors in LEAD-specific atherothrombosis using Apoe^-/- mice fed with normal chow or western type diet.

Second part of this project is centered on LEAD-specific calcification. Arterial calcification in atherosclerotic lesions is an independent risk factor for cardiovascular mortality. Microcalcifications in the fibrous cap can increase the risk of plaque rupture. In contrast, lesions with a high calcific burden results in more stable plaque phenotype. Arterial calcification in LEAD could lead to arterial stiffness, which can influence diagnostic parameters like ABI measurement and clinical interventions leading to failure of endovascular repair. Therefore, our second aim is to understand the mechanisms involved in LEAD-specific calcification that could enable us to unravel potential therapeutic targets to reduce its clinical impact.

Anais Yerly: Unravel the cell specific role of ACKR3 in Atherosclerosis

Compared to the widely studied classical chemokine receptors, the lesser-known atypical chemokine receptor (ACKR)s bind chemokines with high affinity and do not induce G-protein coupled signalling. Nonetheless, they can modulate the chemokines system by scavenging, transporting and storing chemokines as well as forming heterodimer with canonical chemokine receptors.  ACKR3 was recently found to be expressed on leukocytes, including macrophages and marginal B cells. However, the role of ACKR3 in CVD remains mostly unknown.  In this study, we aim to investigate ACKR3 on macrophages, the main cell-mediated driver of atherosclerosis, and B cells which are both pro-atherogenic and atheroprotective depending on their subsets. Atherosclerotic mouse models will be used to study cell-specific ACKR3 loss of function (inducible Cre-Lox system) in monocytes/macrophages and B cells. With this project, we aim to understand the implication and function of ACKR3 on macrophages and B cells in atherosclerosis development and inflammatory responses.