Atherosclerosis is a chronic inflammatory disease of the large arteries that occurs under hyperlipidemic conditions. Mononuclear cells are crucially involved in all stages of atherosclerosis, from plaque development and progression to destabilization. Circulating mononuclear cells get imprinted with information on disease progress. The circulating cells biobank, which we coordinate, already contains elaborate data on patient specific inflammatory cell phenotyping (e.g. by flow cytometry, mRNA profile, miRNA, and DNA from PBMCs or specific fractioned cell types. B cells have classically been defined as protective for atherosclerosis due to their ability to produce auto-antibodies to oxLDL. However, it has become increasingly clear that B cells carry out both pro- and anti-atherogenic functions. As part of the Athero B Cell consortium we characterized the B cell subtype distribution in atherosclerotic patients (from the Athero Express biobank) and map B cell-related changes associated specifically with cardiovascular disease. This information can be used to improve disease diagnosis and may provide lead targets for therapeutic intervention.
Atheroprotective and atherogenic effects of different B Cell subtypes
Saskia de Jager, Imo Hofer, John Meeuwsen, Marian Wesseling, Judith de Haan,
Lena Bosch and Maike Brans.
Inflammation and Cardiac Fibrosis:
Heart failure is increasing as patients initially survive hypertension, acute myocardial infarction, valvular disease and other cardiac challenges to later progress to chronic HF. Although it is generally accepted that inflammation is an important determinant of HF, therapy based on reducing inflammation does not exist at this point. We demonstrated that not only the cardiomyocyte but also the circulating leukocyte is a prominent player in immune activation after MI and during HF. Apart from their immunemodulatory role, inflammatory cells have also been implicated in (autoimmune) fibrotic diseases. Our research focuses on the inflammatory response in the development of heart failure with preserved ejection fraction (HFpEF), with specific emphasis on immune regulated fibrosis of the myocardium.
Research Support and resources:
- FP7 Athero-B-Cell, Consortium member
- Queen of Hearts (Dutch Heart Foundation), WP leader
- EnCare Biotech, Manager Research
- CVON RECONNECT, Consortium member
Key publications of our group:
- Frodermann V et al. J Immunol. 2015;194(5):2208.
- de Hoog VC et al. Cardiovascular Research 2015;108(3):367.
- Willems et al. PLoS One. 2014;9(2):e88984.
- de Jager SC et al. Arterioscler Thromb Vasc Biol. 2013;33(12):2810-7.
- de Jager SC et al. J Exp Med. 2011;208(2):217.
- de Jager SC et al. J Mol Cell Cardiol. 2008;45(3):446.