Experimental Vascular Pathology

CONTEXT

Atherosclerosis is a progressive vascular disease driven by excessive lipid accumulation, chronic inflammation, and aberrant tissue remodeling. Manifesting clinically in its advanced stages, it is the leading cause of ischemic heart diseases. Despite substantial advancements in diagnostics and treatment, the global burden of atherosclerosis continues to rise, due to the widespread adoption of "Western" lifestyle factors. This underscores the urgent need for complementary therapies targeting underexplored disease mechanisms.

OUR MISSION AND APPROACH

The Experimental Vascular Pathology (EVP) group at UM leverages cutting-edge single-cell and spatial omics technologies to uncover novel disease-driving mechanisms in human vascular ageing and atherosclerosis. A central focus of our research lies in unraveling how comorbidities such as type 2 diabetes (T2D) exacerbate disease progression. Promising candidate mechanisms are validated through advanced histological methods, human in vitro systems, and murine in vivo models, laying a foundation for innovative therapeutic interventions.

EVP TECHNOLOGIES

Our group is equipped with state-of-the-art tools and routinely employs the following resources:

• Comprehensive Cohorts: Well-documented datasets, including carotid plaque tissue (MaasHPS, n=800), brain thrombosuction tissue (InBrain&Heart cohort, n=220), plasma and blood samples (CTMM Circulating Cells, n=500), complemented by integrated datasets from open-access repositories.

• Single-cell RNA-sequencing technology

• Advanced bioinformatics pipelines

• High-resolution microscopy: Multiplex cyclic and spectral immunofluorescence imaging

• High-throughput functional screening platforms for macrophages (MacroScreen), fibroblasts (Fibroscreen), and macrophage-fibroblast interactions

• Unique flow cytometry methods for metabolic profiling (e.g., SCENITH, Met-His)

• Murine models for atherosclerosis, vascular ageing and fibroblast lineage tracking and depletion

• Spatial metabolomics using mass spectrometry imaging

• Antibody and peptide phage display for lead development

FOCUS AREAS

Our research efforts are organized into four core lines of inquiry:

1.      Targeting fibroblast diversity to address vascular aging and atherosclerosis (PI: Judith Sluimer)

2.  Metabolic modulation of disease-associated macrophages in human (diabetic) atherosclerosis (PI: Erik Biessen)

3.  Imaging macrophage phenotypic and functional heterogeneity in its tissue micro-environment (PI: Pieter Goossens)

4.  Deciphering mechanisms of chronic kidney disease (CKD)-accelerated atherosclerosis (PIs: Joachim Jankowski & Emiel van der Vorst)

For more details on these focus areas, please visit the pages of the respective PIs.