Journal ArticleDOI
Effect of cholesterol crystals on plaques and intima in arteries of patients with acute coronary and cerebrovascular syndromes.
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TLDR
By avoiding ethanol in tissue preparation, CCs perforating the intima were shown to be associated with PD, and crystal content was significantly associated with clinical events, suggesting that cholesterol crystallization may have a role in PD.Abstract:
Plaque disruption (PD) causes most acute cardiovascular events. Although cholesterol crystals (CCs) have been observed in plaques, their role in PD was unknown. However, cholesterol expands with crystallization tearing and perforating fibrous tissues. This study tested the hypothesis that CCs can damage plaques and intima, triggering PD, as observed in tissues prepared without ethanol solvents that dissolve CCs. Coronary arteries of patients who died of acute coronary syndrome (n = 19) and non–acute coronary syndrome causes (n = 12) and carotid plaques from patients with (n = 51) and without (n = 19) neurologic symptoms were studied. Samples were examined for CCs perforating the intima using light and scanning electron microscopy (SEM) with ethanol or vacuum dehydration. In addition, fresh unfixed carotid plaques were examined at 37°C using confocal microscopy. Crystal content using SEM was scored from 0 to +3. SEM using vacuum dehydration had significantly higher crystal content compared with SEM using ethanol dehydration (+2.5 ± 0.53 vs +0.25 ± 0.46; pread more
Citations
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Journal ArticleDOI
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Peter Duewell,Hajime Kono,Katey J. Rayner,Katey J. Rayner,Cherilyn M. Sirois,Gregory I. Vladimer,Franz Bauernfeind,George S. Abela,Luigi Franchi,Guillermo Gabriel Nuñez,Max Schnurr,Terje Espevik,Egil Lien,Katherine A. Fitzgerald,Kenneth L. Rock,Kathryn J. Moore,Kathryn J. Moore,Samuel D. Wright,Veit Hornung,Eicke Latz,Eicke Latz +20 more
TL;DR: It is shown that cholesterol crystals activate the NLRP3 inflammasome in phagocytes in vitro in a process that involves phagolysosomal damage and that crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation.
Journal ArticleDOI
Cholesterol Crystals Activate the NLRP3 Inflammasome in Human Macrophages: A Novel Link between Cholesterol Metabolism and Inflammation
Kristiina Rajamäki,Jani Lappalainen,Katariina Öörni,Elina Välimäki,Sampsa Matikainen,Petri T. Kovanen,Kari K. Eklund +6 more
TL;DR: It is shown that human macrophages avidly phagocytose cholesterol crystals and store the ingested cholesterol as cholesteryl esters, and cholesterol crystals induced dose-dependent secretion of mature IL-1β from human monocytes and macrophage.
Journal ArticleDOI
Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel
Jan Borén,M. John Chapman,M. John Chapman,Ronald M. Krauss,Chris J. Packard,Jacob F. Bentzon,Jacob F. Bentzon,Christoph J. Binder,Mat J.A.P. Daemen,Linda L. Demer,Robert A. Hegele,Stephen J. Nicholls,Børge G. Nordestgaard,Gerald F. Watts,Gerald F. Watts,Eric Bruckert,Sergio Fazio,Brian A. Ference,Brian A. Ference,Ian D. Graham,Jay D. Horton,Ulf Landmesser,Ulrich Laufs,Luis Masana,Gerard Pasterkamp,Frederick J. Raal,Kausik K. Ray,Heribert Schunkert,Marja-Riitta Taskinen,Bart van de Sluis,Olov Wiklund,Lale Tokgozoglu,Alberico L. Catapano,Henry N. Ginsberg +33 more
TL;DR: In this paper, the authors proposed a method to solve the problem of the problem: this paper ] of "uniformity" of the distribution of data points in the data set.
Journal ArticleDOI
The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles.
TL;DR: The medial VSMC is the organizer of the inwardly directed angiogenic response arising from the adventitia by overexpressing vascular endothelial growth factor in response to lipid-stimulated peroxisome proliferator-activated receptor-γ, and probably also the organizers of the adventitial immune response by secreting chemokines.
Journal ArticleDOI
NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis.
TL;DR: The mechanisms of NLRP3 inflammasome activation and proinflammatory IL-1 family cytokine production in the context of atherosclerosis are reviewed and treatment possibilities are discussed in light of the positive outcomes of the CANTOS trial.
References
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Journal ArticleDOI
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