Mediators, Metabolites and Atypical Immune Cells in Cardiovascular Disease
Författare
Summary, in English
In Paper I we investigated associations between the leukocyte guiding chemokines CCL21 and CCL19 and incident coronary events in the general population-based Malmö Diet and Cancer cohort. We found that high plasma levels of CCL21, but not CCL19, had an independent association to incident coronary events. High levels of CCL19 were on the other hand associated with both incident heart failure and mortality.
In Paper II we investigated the effect of drinking water supplementation with α-ketoglutarate or glutamine on atherosclerosis development and plaque composition. Our main finding was that glutamine, an important fuel source for immune cells, caused increased development of atherosclerosis in male mice. These mice also had larger accumulation of cells, including neutrophils, in the adventitia surrounding the aorta.
In Paper III we investigated CD21low age-associated B cells (ABCs), previously identified in atherosclerotic plaques. We evaluated their clonality, differentiation potential and effect on atherosclerosis development. In humans we investigated if CD21low ABCs were associated to incident coronary events. We found that CD21low ABCs were clonally expanded and could differentiate into plasma cells in vivo. CD21low ABCs also aggravated murine atherosclerosis and high numbers of circulating CD21low ABCs were associated with incident coronary events in humans.
In Paper IV we investigated if, as suggested by animal studies, invariant natural killer T (iNKT) cells have an association to incident coronary events in humans. However, high numbers of these lipid-specific cells did not have an association to incident coronary events. Furthermore, we identified a subpopulation of iNKT cells that were CD4-CD8- which had an independent, inverse association to incident coronary events.
In conclusion, this thesis illustrates the multifaceted contributions of inflammatory mediators and cells in CVD and atherosclerosis, while also providing novel insights into this important research field.
Avdelning/ar
Publiceringsår
2024
Språk
Engelska
Publikation/Tidskrift/Serie
Lund University, Faculty of Medicine Doctoral Dissertation Series 2024:121
Issue
2024:121
Fulltext
- Available as PDF - 16 MB
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Dokumenttyp
Doktorsavhandling
Förlag
Lund University, Faculty of Medicine
Ämne
- Immunology in the medical area
Nyckelord
- Cardiovascular disease
- Atherosclerosis
- Immunology
- Metabolism
- Age-associated B cells
- Invariant natural killer T cells
- Coronary events
- Immunometabolism
Aktiv
Published
Forskningsgrupp
- Cardiovascular Research - Cellular Metabolism and Inflammation
ISBN/ISSN/Övrigt
- ISSN: 1652-8220
- ISBN: 978-91-8021-617-3
Försvarsdatum
11 oktober 2024
Försvarstid
09:00
Försvarsplats
Segerfalksalen, BMC A10, Sölvegatan 17 i Lund
Opponent
- Åsa Tivesten (Professor)