The natural history of human atherosclerosis : a histopathological approach

Abstract

This thesis systematically evaluates the critical morphological, pathophysiological and immunological aspects of the human atherosclerotic process using a unique biobank containing over 500 individual peri-renal abdominal aortic wall patches and over 600 coronary artery segments of the left coronary artery. The aortic patches were obtained during liver, kidney or pancreas transplantation and the coronary artery segments were collected from healthy human hearts that were retrieved from Dutch post-mortem donors within 24 hours after circulatory stop and brought to the National Heart Valve for heart valve donation. Contrary to other histological studies investigating mechanistic insight into the atherosclerotic process, we used tissue from a group of apparently healthy individuals with an equal age and sex distribution, thereby avoiding potential bias introduced by the use of autopsy material from coronary death victims (mostly either young or old patients) or by the use of material from patients undergoing vascular surgery (generally end-stage atherosclerotic disease). The primary aim of this thesis was to explore the natural history of human aortic atherosclerosis in order to gain more insight in the pathophysiology of plaque development and unstable culprit lesion formation that potentially gives rise to the clinical manifestations of atherosclerosis.