|
Title
|
|
|
|
Caspase-3 deletion promotes necrosis in atherosclerotic plaques of ApoE knockout mice
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| Apoptosis of macrophages and vascular smooth muscle cells (VSMCs) in advanced atherosclerotic plaques contributes to plaque progression and instability. Caspase-3, a key executioner protease in the apoptotic pathway, has been identified in human and mouse atherosclerotic plaques but its role in atherogenesis is not fully explored. We therefore investigated the impact of caspase- 3 deletion on atherosclerosis by crossbreeding caspase-3 knockout (Casp3−/−) mice with apolipoprotein E knockout (ApoE−/−) mice. Bonemarrow-derivedmacrophages and VSMCs isolated from Casp3−/−ApoE−/− mice were resistant to apoptosis but showed increased susceptibility to necrosis. However, caspase-3 deficiency did not sensitize cells to undergo RIP1-dependent necroptosis. To study the effect on atherosclerotic plaque development, Casp3+/+ApoE−/− and Casp3−/−ApoE−/− mice were fed a western-type diet for 16 weeks. Though total plasma cholesterol, triglycerides, and LDL cholesterol levels were not altered, both the plaque size and percentage necrosis were significantly increased in the aortic root of Casp3−/−ApoE−/− mice as compared to Casp3+/+ApoE−/− mice.Macrophage contentwas significantly decreased in plaques of Casp3−/−ApoE−/− mice as compared to controls, while collagen content and VSMC content were not changed. To conclude, deletion of caspase-3 promotes plaque growth and plaque necrosis in ApoE−/− mice, indicating that this antiapoptotic strategy is unfavorable to improve atherosclerotic plaque stability. 1. Introduction |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Oxidative medicine and cellular longevity
| |
|
Publication
|
|
|
|
2017
| |
|
ISSN
|
|
|
|
1942-0900
1942-0994
| |
|
DOI
|
|
|
|
10.1155/2016/3087469
| |
|
Volume/pages
|
|
|
|
240
(2017)
, p. 1024-1035
| |
|
Article Reference
|
|
|
|
3087469
| |
|
ISI
|
|
|
|
000390779400001
| |
|
Medium
|
|
|
|
E-only publicatie
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|
Full text (open access)
|
|
|
|
| |
|