Characterization of age-associated immunity in atherosclerosis

Smit, V. (2024)

Doctoral Thesis

Healthy aging is one of the prime goals in today's society and atherosclerosis is among the greatest causes of morbidity in elderly. Cardiovascular disease patients receiving treatment are often of advanced aged and have an aged immune system, which limits translating experimental findings to the patient. It is therefore essential to take aging into consideration when investigating immune cells and their responses in atherosclerosis studies. This thesis describes research exploring the impact of aging on the immunological landscape in atherosclerotic cardiovascular disease using single-cell profiling. Through the use of a highly translational aging mouse model of atherosclerosis, we characterized inflammation in the plaques of young versus old mice. We discovered new cell types (T and B cells) not present in young mice with atherosclerosis. These cells secrete a variety of inflammatory factors that may contribute to the disease process and exacerbate arteriosclerosis. While the aged B cell is more prevalent in female mice, the aged T cell is more abundant in male mice. We then also found these aged cells in the blood and plaques of cardiovascular disease patients. These aged cell types could be interesting targets for future treatments against progression of atherosclerotic cardiovascular disease.

• Cardiovascular disease
• Atherosclerosis
• Aging
• Sex
• Immunology
• Immunosenescence
• Single-cell transcriptomics

• All authors: Smit, V.
• Supervisor: Foks, A.C.; Kuiper, J.; Bot, I.
• Committee: Irth, H.; Lange, E.C.M. de; Winther, M.P.J. de; Binder, C.J.; Westerterp, M.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Academic Centre for Drug Research (LACDR), Faculty of Science, Leiden University
• Date: 2024-09-12
• ISBN (print): 9789465101279
• Sponsorship: Dutch Heart Foundation