Cardiovascular immunology and metabolism

Cardiovascular immunology and metabolism

Cardiovascular diseases (CVDs) are the leading cause of mortality and disability worldwide, imposing a significant burden on society. Coronary heart disease and cerebrovascular disease, the two most common forms of cardiovascular disease, are caused by acute complications of atherosclerosis. CVD kills over 17 million individuals every year, which accounts for one third of all global deaths.

Although population-wide management of traditional risk factors for CVDs (e.g. hyperlipidemia, high-blood pressure, glycaemia) has reduced the incidence of cardiovascular events in developed countries, substantial residual risk remains. Thus, translational therapeutic strategies targeting novel molecular pathways regulating atherosclerosis are needed. 

Atherosclerosis is a chronic inflammatory disease initiated by retention and accumulation of lipids in the artery wall, especially low-density lipoprotein (LDL), leading to maladaptive responses of innate and adaptive immune cells. Notably, metabolism and activation are fully integrated in immune cells, and systemic or microenvironmental changes in metabolism have been shown to modulate their responses.

In pioneer work, we have identified several targets to modulate the unwanted immune responses in the artery wall, including components of LDL that can trigger innate and adaptive immune cells, and metabolites of the essential amino acid tryptophan, via the Kynurenine pathway. Our research indicates that metabolites are not just ‘fuels’ in their metabolic pathways, but that they can also act as signalling molecules in immune cells and influence atherosclerosis. By increasing the understanding of the immunometabolic reactions controlling immune responses in atherogenesis, our research will lead to the development of new drugs to treat and prevent atherosclerotic CVDs.

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Group leader

Daniel Ketelhuth

E-mail

daniel.ketelhuth@ki.se

Job title

Associate Professor

House

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Research

Biomarkers, Circulation and respiration, Endocrinology and metabolism

Disease

Atherosclerosis, Cardiovascular diseases, Diabetes

Competence/titles

Adaptive immunity, Amino acids, Animal models, Antibodies, Artery, B-cells, Biochemistry, Cell culture, Drug development, Flow cytometry, Gene expression, Heart, Immunohistochemistry, Immunometabolism, Innate immunity, Lipoproteins, Liver, Macrophage/Microglia/Monocryte/APC, Memory, Mess spectrometry, Metabolism, Molecular, Pathology, Protein expression, Proteins, Proteomics, T-cells, Transcription, Translational, Tryptophan, Vaccines