Atherosclerotic Plaque Vulnerability in Experimental Models of Atherosclerosis
(Instabiliteit van Atherosclerotische Plaques in Experimentele Modellen van Atherosclerose)
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Atherosclerosis is a chronic and often progressive disease of the wall of the arterial vasculature. The term atherosclerosis is derived from the Greek words “athero” meaning gruel or paste and “skleros” meaning stiff or hard. Atherosclerosis is considered a major clinical problem, which underlies most ischemic events of both the heart as well as the brain. It is the result of the Western lifestyle and can start very early in life even in persons without a strong genetic disposition like untreated familial hypercholesteremia. From the second decade onwards, the disease progresses more rapidly. The clinical silence of atherosclerosis is often broken between the 3rd and 5th decade, when patients present with ischemic complaints of e.g. heart and brain. Despite the continuing decrease in cardiovascular disease (CVD) associated death over the last decade, it still is one of the main causes of death in The Netherlands, accounting for 30,7% of total deaths in 2007. As a result, the socio-economic consequences remain huge. It has been estimated that in the European Union annual CVD-associated costs are €169 billion, of which €105 billion are costs directly related to healthcare. Historically, atherosclerosis was simply considered as an accumulation of lipids in the vascular wall. In the late 90’s, Russell Ross proposed a major revision of this theory, and these days the perspective of atherosclerosis as a complicated lipid-driven inflammatory disease is widely accepted. Lipid metabolism and inflammation mutually influence each other yielding the complete spectrum of atherosclerotic disease progression. This is reflected in the correlation between future cardiovascular events and the combined values of cholesterol, as indicator of lipid status, and CRP, as indicator of systemic inflammatory activity. Since CRP levels reflect systemic inflammatory activity, this notion underscores the role of immunity in human atherosclerosis.
Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged. Additional financial contribution to the publication of this thesis was provided by: Novartis, St. Jude Medical Nederland B.V., Servier Nederland Farma B.V., Holland Medical, Boehringer Ingelheim B.V. Guerbet Nederland B.V. , MSD Nederland B.V..
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