CCN4 (WISP-1) reduces apoptosis and atherosclerotic plaque burden in an ApoE mouse model.

Autor: Williams H; Bristol Heart Institute, Bristol Medical School, University of Bristol, UK. Electronic address: helen.williams@bristol.ac.uk., Simmonds S; KU Leuven, Belgium., Bond A; Bristol Heart Institute, Bristol Medical School, University of Bristol, UK., Somos A; Bristol Heart Institute, Bristol Medical School, University of Bristol, UK., Li Z; Bristol Heart Institute, Bristol Medical School, University of Bristol, UK., Forbes T; Bristol Heart Institute, Bristol Medical School, University of Bristol, UK., Bianco R; Bristol Heart Institute, Bristol Medical School, University of Bristol, UK., Dugdale C; Flow Cytometry Facility, School of Cellular & Molecular Medicine, University of Bristol, UK., Brown Z; Flow Cytometry Facility, School of Cellular & Molecular Medicine, University of Bristol, UK., Rice H; Flow Cytometry Facility, School of Cellular & Molecular Medicine, University of Bristol, UK., Herman A; Flow Cytometry Facility, School of Cellular & Molecular Medicine, University of Bristol, UK., Johnson J; Bristol Heart Institute, Bristol Medical School, University of Bristol, UK., George S; Bristol Heart Institute, Bristol Medical School, University of Bristol, UK.
Jazyk: angličtina
Zdroj: Atherosclerosis [Atherosclerosis] 2024 Oct; Vol. 397, pp. 118570. Date of Electronic Publication: 2024 Aug 26.
DOI: 10.1016/j.atherosclerosis.2024.118570
Abstrakt: Background and Aims: CCN4/WISP-1 regulates various cell behaviours that contribute to atherosclerosis progression, including cell adhesion, migration, proliferation and survival. We therefore hypothesised that CCN4 regulates the development and progression of atherosclerotic plaques.
Methods: We used a high fat fed ApoE -/- mouse model to study atherosclerotic plaque progression in the brachiocephalic artery and aortic root. In protocol 1, male ApoE -/- mice with established plaques were given a CCN4 helper-dependent adenovirus to see the effect of treatment with CCN4, while in protocol 2 male CCN4 -/- ApoE -/- were compared to CCN4 +/+ ApoE -/- mice to assess the effect of CCN4 deletion on plaque progression.
Results: CCN4 overexpression resulted in reduced occlusion of the brachiocephalic artery with less apoptosis, fewer macrophages, and attenuated lipid core size. The amount of plaque found on the aortic root was also reduced. CCN4 deficiency resulted in increased apoptosis and occlusion of the brachiocephalic artery as well as increased plaque in the aortic root. Additionally, in vitro cells from CCN4 -/- ApoE -/- mice had higher apoptotic levels. CCN4 deficiency did not significantly affect blood cholesterol levels or circulating myeloid cell populations.
Conclusions: We conclude that in an atherosclerosis model the most important action of CCN4 is the effect on cell apoptosis. CCN4 provides pro-survival signals and leads to reduced cell death, lower macrophage number, smaller lipid core size and reduced atherosclerotic plaque burden. As such, the pro-survival effect of CCN4 is worthy of further investigation, in a bid to find a therapeutic for atherosclerosis.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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