Leiden University Scholarly Publications

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Reilly, N.A. (2024)

The effects of triglycerides and fatty acids on T cells: role in atherosclerosis

Doctoral Thesis
Atherosclerosis, a leading cause of cardiovascular disease, is characterized by lipid accumulation in blood vessel walls. This chronic inflammation leads to plaque formation, increasing the risk of heart attacks and strokes. While traditionally linked to cholesterol and macrophages, emerging research highlights the roles of triglycerides and T cells in atherosclerosis development. Triglycerides can exacerbate the disease, while T cells are among the most abundant immune cells in atherosclerotic plaques.
This thesis investigates how triglycerides and fatty acids influence T cell function, employing in vitro, -omics, and in vivo methods. It maps the effects of various fatty acids on T cell metabolism, activation, and differentiation. Notably, in vitro exposure to oleic acid resulted in a pro-inflammatory transcriptomic profile in CD4+ T cells, enhancing the likelihood of differentiation into IL-9 producing cells, linked to atherosclerosis pathogenesis. In contrast,...Show moreAtherosclerosis, a leading cause of cardiovascular disease, is characterized by lipid accumulation in blood vessel walls. This chronic inflammation leads to plaque formation, increasing the risk of heart attacks and strokes. While traditionally linked to cholesterol and macrophages, emerging research highlights the roles of triglycerides and T cells in atherosclerosis development. Triglycerides can exacerbate the disease, while T cells are among the most abundant immune cells in atherosclerotic plaques.
This thesis investigates how triglycerides and fatty acids influence T cell function, employing in vitro, -omics, and in vivo methods. It maps the effects of various fatty acids on T cell metabolism, activation, and differentiation. Notably, in vitro exposure to oleic acid resulted in a pro-inflammatory transcriptomic profile in CD4+ T cells, enhancing the likelihood of differentiation into IL-9 producing cells, linked to atherosclerosis pathogenesis. In contrast, eicosapentaenoic acid showed strong anti-inflammatory transcriptomics. Finally, a natural in vivo experiment revealed a pro-inflammatory transcriptomic profile in T cells from individuals with elevated triglyceride levels as compared to those without. This work opens new avenues for further research and enhances our understanding of the intricate relationship between fatty acids, triglycerides and T cells, which effects on how we understand human health and disease.
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Triglycerides
T cells
Fatty acids
Eicosapentaenoic acid
Oleic acid
Palmitic acid
Hypertriglyceridemia
Atherosclerosis
Cardiovascular disease
Immunometabolism
All authors
Reilly, N.A.
Supervisor
Heijmans, B.T.; Jukema, J.W.
Committee
Rensen, P.C.N.; Slagboom, P.E.; Bot, I.; Van den Bossche, J.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2024-10-30
ISBN (print)
9789493391543

Funding

Sponsorship
The research described in this thesis was supported by the Dutch CardioVascular Alliance (The Dutch Heart Foundation, Dutch Federation of University Medical Centres, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences) for the GENIUSII project Generating the Best Evidence-Based Pharmaceutical Targets for Atherosclerosis (CVON2011-19 and CVON2017-20).