Three-Dimensional Imaging Provides Detailed Atherosclerotic Plaque Morphology and Reveals Angiogenesis After Carotid Artery Ligation

被引:28
作者
Becher, Tobias [1 ,6 ,7 ]
Riascos-Bernal, Dario F. [3 ]
Kramer, Daniel J. [1 ]
Almonte, Vanessa M. [3 ]
Chi, Jingy [1 ]
Tong, Tao [2 ]
Oliveira-Paula, Gustavo H. [3 ]
Koleilat, Issam [5 ]
Chen, Wei [4 ,8 ]
Cohen, Paul [1 ]
Sibinga, Nicholas E. S. [3 ]
机构
[1] Rockefeller Univ, Lab Mol Metab, 1230 York Ave,POB 223, New York, NY 10065 USA
[2] Rockefeller Univ, Bioimaging Resource Ctr, 1230 York Ave, New York, NY 10021 USA
[3] Albert Einstein Coll Med, Wilf Family Cardiovasc Res Inst, Dept Dev & Mol Biol, Dept Med, Bronx, NY 10467 USA
[4] Albert Einstein Coll Med, Dept Med, Nephrol Div, Bronx, NY 10467 USA
[5] Montefiore Med Ctr, Dept Cardiothorac & Vasc Surg, Div Vasc Surg, 111 E 210th St, Bronx, NY 10467 USA
[6] DZHK German Ctr Cardiovasc Res, Partner Site Heidelberg Mannheim, Mannheim, Germany
[7] Univ Med Ctr Mannheim, Dept Med, Div Cardiol, Mannheim, Germany
[8] Univ Rochester, Sch Med & Dent, Dept Med, Rochester, NY 14627 USA
基金
美国国家卫生研究院;
关键词
3-D imaging; atherosclerosis; carotid arteries; endothelium; neointima; vascular remodeling; CORONARY ATHEROSCLEROSIS; NEOINTIMA FORMATION; MOUSE MODEL; INJURY; MICE; RECRUITMENT; CONTRAST; DISEASE; STRESS; CELL;
D O I
10.1161/CIRCRESAHA.119.315804
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Rationale: Remodeling of the vessel wall and the formation of vascular networks are dynamic processes that occur during mammalian embryonic development and in adulthood. Plaque development and excessive neointima formation are hallmarks of atherosclerosis and vascular injury. As our understanding of these complex processes evolves, there is a need to develop new imaging techniques to study underlying mechanisms. Objective: We used tissue clearing and light-sheet microscopy for 3-dimensional (3D) profiling of the vascular response to carotid artery ligation and induction of atherosclerosis in mouse models. Methods and Results: Adipo-Clear and immunolabeling in combination with light-sheet microscopy were applied to image carotid arteries and brachiocephalic arteries, allowing for 3D reconstruction of vessel architecture. Entire 3D neointima formations with different geometries were observed within the carotid artery and scored by volumetric analysis. Additionally, we identified a CD31-positive adventitial plexus after ligation of the carotid artery that evolved and matured over time. We also used this method to characterize plaque extent and composition in the brachiocephalic arteries of ApoE-deficient mice on high-fat diet. The plaques exhibited inter-animal differences in terms of plaque volume, geometry, and ratio of acellular core to plaque volume. A 3D reconstruction of the endothelium overlying the plaque was also generated. Conclusions: We present a novel approach to characterize vascular remodeling in adult mice using Adipo-Clear in combination with light-sheet microscopy. Our method reconstructs 3D neointima formation after arterial injury and allows for volumetric analysis of remodeling, in addition to revealing angiogenesis and maturation of a plexus surrounding the carotid artery. This method generates complete 3D reconstructions of atherosclerotic plaques and uncovers their volume, geometry, acellular component, surface, and spatial position within the brachiocephalic arteries. Our approach may be used in a number of mouse models of cardiovascular disease to assess vessel geometry and volume.
引用
收藏
页码:619 / 632
页数:14
相关论文
共 47 条
[1]  
Benjamin EJ, 2019, CIRCULATION, V139, pE56, DOI [10.1161/CIR.0000000000000746, 10.1161/CIR.0000000000000659]
[2]   Lineage tracking of origin and fate of smooth muscle cells in atherosclerosis [J].
Bentzon, Jacob F. ;
Majesky, Mark W. .
CARDIOVASCULAR RESEARCH, 2018, 114 (04) :492-500
[3]   Ultra-high-resolution 3D imaging of atherosclerosis in mice with synchrotron differential phase contrast: a proof of concept study [J].
Bonanno, Gabriele ;
Coppo, Simone ;
Modregger, Peter ;
Pellegrin, Maxime ;
Stuber, Annina ;
Stampanoni, Marco ;
Mazzolai, Lucia ;
Stuber, Matthias ;
van Heeswijk, Ruud B. .
SCIENTIFIC REPORTS, 2015, 5
[4]   Contrast enhancement in atherosclerosis development in a mouse model:: in vivo results at 2Tesla [J].
Chaabane, L ;
Pellet, N ;
Bourdillon, MC ;
Mansard, CD ;
Sulaiman, A ;
Hadour, G ;
Thivolet-Béjui, F ;
Roy, P ;
Briguet, A ;
Douek, P ;
Soulas, EC .
MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE, 2004, 17 (3-6) :188-195
[5]   Adipo-Clear: A Tissue Clearing Method for Three-Dimensional Imaging of Adipose Tissue [J].
Chi, Jingyi ;
Crane, Audrey ;
Wu, Zhuhao ;
Cohen, Paul .
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2018, (137)
[6]   Three-Dimensional Adipose Tissue Imaging Reveals Regional Variation in Beige Fat Biogenesis and PRDM16-Dependent Sympathetic Neurite Density [J].
Chi, Jingyi ;
Wu, Zhuhao ;
Choi, Chan Hee J. ;
Lily Nguyen ;
Tegegne, Saba ;
Ackerman, Sarah E. ;
Crane, Audrey ;
Marchildon, Francois ;
Tessier-Lavigne, Marc ;
Cohen, Paul .
CELL METABOLISM, 2018, 27 (01) :226-+
[7]   Developmental and Pathological Angiogenesis [J].
Chung, Alicia S. ;
Ferrara, Napoleone .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 27, 2011, 27 :563-584
[8]   Plaque Rupture in Coronary Atherosclerosis Is Associated With Increased Plaque Structural Stress [J].
Costopoulos, Charis ;
Huang, Yuan ;
Brown, Adam J. ;
Calvert, Patrick A. ;
Hoole, Stephen P. ;
West, Nick E. J. ;
Gillard, Jonathan H. ;
Teng, Zhongzhao ;
Bennett, Martin R. .
JACC-CARDIOVASCULAR IMAGING, 2017, 10 (12) :1472-1483
[9]   Acute Coronary Syndromes The Way Forward From Mechanisms to Precision Treatment [J].
Crea, Filippo ;
Libby, Peter .
CIRCULATION, 2017, 136 (12) :1155-1166
[10]   Light-sheet Fluorescence Microscopy for the Study of the Murine Heart [J].
Ding, Yichen ;
Bailey, Zachary ;
Messerschmidt, Victoria ;
Nie, Jun ;
Bryant, Richard ;
Rugonyi, Sandra ;
Fei, Peng ;
Lee, Juhyun ;
Hsiai, Tzung K. .
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2018, (139)