Angiopoietin-2 blocking antibodies reduce early atherosclerotic plaque development in mice

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Theelen , T L , Lappalainen , J P , Sluimer , J C , Gurzeler , E , Cleutjens , J P , Gijbels , M J , Biessen , E A L , Daemen , M J A P , Alitalo , K & Yla-Herttuala , S 2015 , ' Angiopoietin-2 blocking antibodies reduce early atherosclerotic plaque development in mice ' , Atherosclerosis , vol. 241 , no. 2 , pp. 297-304 . https://doi.org/10.1016/j.atherosclerosis.2015.05.018

Title: Angiopoietin-2 blocking antibodies reduce early atherosclerotic plaque development in mice
Author: Theelen, Thomas L.; Lappalainen, Jari P.; Sluimer, Judith C.; Gurzeler, Erika; Cleutjens, Jack P.; Gijbels, Marion J.; Biessen, Erik A. L.; Daemen, Mat J. A. P.; Alitalo, Kari; Yla-Herttuala, Seppo
Other contributor: University of Helsinki, Research Programs Unit


Date: 2015-08
Language: eng
Number of pages: 8
Belongs to series: Atherosclerosis
ISSN: 0021-9150
DOI: https://doi.org/10.1016/j.atherosclerosis.2015.05.018
URI: http://hdl.handle.net/10138/203740
Abstract: Objective: Angiopoietin-2 (Ang-2) blocking agents are currently undergoing clinical trials for use in cancer treatment. Ang-2 has also been associated with rupture-prone atherosclerotic plaques in humans, suggesting a role for Ang-2 in plaque stability. Despite the availability of Ang-2 blocking agents, their clinical use is still lacking. Our aim was to establish if Ang-2 has a role in atheroma development and in the transition of subclinical to clinically relevant atherosclerosis. We investigated the effect of antibody-mediated Ang-2 blockage on atherogenesis after in a mouse model of atherosclerosis. Methods: Hypercholesterolemic (low-density lipoprotein receptor(-/-) apolipoprotein B-100/100) mice were subjected to high-cholesterol diet for eight weeks, one group with and one group without Ang-2 blocking antibody treatment during weeks 4-8. To enhance plaque development, a peri-adventitial collar was placed around the carotid arteries at the start of antibody treatment. Aortic root, carotid arteries and brachiocephalic arteries were analyzed to evaluate the effect of Ang-2 blockage on atherosclerotic plaque size and stable plaque characteristics. Results: Anti-Ang-2 treatment reduced the size of fatty streaks in the brachiocephalic artery (-72%, p <0.05). In addition, antibody-mediated Ang-2 blockage reduced plasma triglycerides (-27%, p <0.05). In contrast, Ang-2 blockage did not have any effect on the size or composition (collagen content, macrophage percentage, adventitial microvessel density) of pre-existing plaques in the aortic root or collar-induced plaques in the carotid artery. Conclusions: Ang-2 blockage was beneficial as it decreased fatty streak formation and plasma triglyceride levels, but had no adverse effect on pre-existing atherosclerosis in hypercholesterolemic mice. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.
Subject: Angiogenesis
Microvascular leakage
Plaque stability
Angiopoietin-2
Atherosclerosis
RECEPTOR TIE-2
CARDIOVASCULAR-DISEASE
MYOCARDIAL-INFARCTION
SERUM ANGIOPOIETIN-2
ANGIOGENIC FACTORS
ENDOTHELIAL-CELLS
HEART-FAILURE
BREAST-CANCER
VEGF
NEOVASCULARIZATION
3111 Biomedicine
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