Leiden University Scholarly Publications

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Ouweneel, A.B. (2019)

Cholesterol metabolism and hematopoiesis interaction in atherothrombosis

Doctoral Thesis
Cardiovascular disease is the leading cause of death worldwide. The primary underlying pathology of cardiovascular disease is atherosclerosis. Atherosclerosis is a chronic, multifactorial disease in which lipid accumulates in the arterial wall, leading to a local inflammatory reaction and atherosclerotic plaque formation. Atherosclerotic disease develops largely asymptomatic over a lifetime. However, plaque rupture or erosion can cause the formation of a superimposed thrombus, blocking the flow of blood, and cause acute cardiovascular events such as myocardial infarction or ischemic stroke. Defects in cholesterol metabolism and hypercholesterolemia, which are major risk factors for atherosclerosis, have been shown to affect hematopoiesis, immune cell production and platelet counts and reactivity. Therefore, bone marrow cholesterol handling is an interesting target in the battle against cardiovascular disease, and acute cardiovascular events in particular. This thesis describes...Show moreCardiovascular disease is the leading cause of death worldwide. The primary underlying pathology of cardiovascular disease is atherosclerosis. Atherosclerosis is a chronic, multifactorial disease in which lipid accumulates in the arterial wall, leading to a local inflammatory reaction and atherosclerotic plaque formation. Atherosclerotic disease develops largely asymptomatic over a lifetime. However, plaque rupture or erosion can cause the formation of a superimposed thrombus, blocking the flow of blood, and cause acute cardiovascular events such as myocardial infarction or ischemic stroke. Defects in cholesterol metabolism and hypercholesterolemia, which are major risk factors for atherosclerosis, have been shown to affect hematopoiesis, immune cell production and platelet counts and reactivity. Therefore, bone marrow cholesterol handling is an interesting target in the battle against cardiovascular disease, and acute cardiovascular events in particular. This thesis describes novel interactions between cholesterol metabolism and the production of immune cells and platelets, and its effects on atherosclerosis and atherothrombosis development.Show less
Atherosclerosis
Atherothrombosis
Hematopoiesis
Megakaryopoiesis
Hypercholesterolemia
Cholesterol efflux
High_density lipoproteins
Mouse models
Small interfering RNA
Protein C
All authors
Ouweneel, A.B.
Supervisor
Eck, M. van
Co-supervisor
Vlijmen, B.J.M. van
Committee
Irth, H.; Bouwstra, J.A.; Versteeg, H.H.; Zelcer, N.; Pasterkamp, G.
Qualification
Doctor (dr.)
Awarding Institution
Leiden Academic Centre for Drug Research (LACDR), Faculty of Science, Leiden University
Date
2019-03-21
ISBN (print)
9789463612340