Aernoud Fiolet

27 General introduction and thesis outline mediated interleukin – 1 release by macrophages identical to other crystal-induced inflammatory responses. 90 The direct relationship with the development of atherosclerosis has been shown using NLRP3, ASC, or interleukin – 1 knockout micemodels.Thesemice have lower inflammatory responses after the development of cholesterol crystals and smaller aortic atherosclerotic lesions. 87 Summarising, the crystallisation of cholesterol plays a pivotal role in the connection between hypercholesterolaemia and the inflammatory response in the developing atherosclerotic lesion. The interplay between cholesterol, inflammation and plaque progression is mediated by a unifying crystal-specific inflammasome pathway. The second role of cholesterol crystals The second local threat to the thinned cap is the puncturing effects of cholesterol crystals. As mentioned above, these effects have sometimes been overlooked due to the methods of conservation and preparation prior to the pathophysiological examination of plaques, since the cholesterol dissipates in the lipid-dissolving ethanol. 91 Alternativemethods of conservation have provided uswith new, detailed information on the atherothrombotic complications associated with, preceded by—and possibly initiated by—cholesterol crystals. The cholesterol crystallisation causes an increase in volume of the plaque. Results of in vitro studies show that the thin cholesterol crystals perforate biological membranes. 92 Indeed, ex vivo case-control studies using scanning electron microscope techniques and vacuum dehydration rather than ethanol dehydration showed that crystals perforated the plaque and intima in patients with acute coronary syndromes but not in those without acute coronary syndromes. 91 The amount of cholesterol crystals is directly related to the serum concentration of cholesterol. 93 In vivo studies in patients with acute coronary syndrome using optical coherence tomography show a higher incidences of thrombosis and plaque rupture in lesions with cholesterol crystals, and their presence is more often seen in those with ST- elevated myocardial infarction. 94,95 With the same technique, cholesterol crystals were observed in a more superficial position in the plaque of patients with acute coronary syndromes compared to the position in those with stable coronary artery disease. 96 Connecting crystals, cytokines, and crevices in the cap Recapitulating, the cholesterol crystal is responsible for two separate mechanisms in the atherothrombotic plaque. Firstly, it is an essential part of the extensive