Atherosclerotic Plaque Destabilization in Mice: A Comparative Study.
Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models.
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
Helene
H
Hartwig
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany.
Carlos
C
Silvestre-Roig
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
Jeffrey
J
Hendrikse
Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
Linda
L
Beckers
Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany.
Nicole
N
Paulin
Department of Cardiology, Biomedical Engineering, Erasmus MC, Rotterdam, The Netherlands.
Kim
K
Van der Heiden
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
Quinte
Q
Braster
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany.
Maik
M
Drechsler
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
Mat J
MJ
Daemen
Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany; Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
Esther
E
Lutgens
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands; Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany; German Centre for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany.
Oliver
O
Soehnlein
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000473:pathology*; D017536:Carotid Artery, Common / Q000473:pathology / Q000601:surgery; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006937:Hypercholesterolemia / Q000473:pathology*; D006978:Hypertension, Renovascular / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000145:classification / Q000473:pathology*; D012077:Renal Artery / Q000473:pathology / Q000601:surgery; D013314:Stress, Mechanical
D001057:Apolipoproteins E