|
Title
|
|
|
|
Altered mitochondrial quality control in Atg7-deficient VSMCs promotes enhanced apoptosis and is linked to unstable atherosclerotic plaque phenotype
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| Vascular smooth muscle cells (VSMCs) are one of the main cellular determinants in arterial pathology. A large body of evidence indicates that death of VSMCs is associated with features of high-risk/vulnerable atherosclerotic plaques. Mitochondrial turnover is an essential aspect of the mitochondrial quality control in which dysfunctional mitochondria are selectively eliminated through autophagy and replaced through expansion of preexisting mitochondria. Even though successful autophagy promotes VSMC survival, it is unclear whether reduced autophagic flux affects mitochondrial quality control of VSMCs in atherosclerotic plaques. By using apolipoprotein E-deficient (ApoE−/−) mice carrying a VSMC-specific deletion of the essential autophagy gene Atg7, we show in the present study that impaired VSMC autophagy promotes an unstable plaque phenotype, as well as the accumulation of fragmented mitochondria with reduced bioenergetic efficiency and more oxidative stress. Furthermore, we demonstrate that disrupted autophagic flux is linked to defective mitophagy and biogenesis of mitochondria, which exacerbate VSMC apoptosis and in turn plaque vulnerability. Overall, our data indicate that mitochondrial quality control is a promising therapeutic target to stabilize atherosclerotic plaques. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Cell Death and Disease. - -
| |
|
Publication
|
|
|
|
2019
| |
|
ISSN
|
|
|
|
2041-4889
| |
|
DOI
|
|
|
|
10.1038/S41419-019-1400-0
| |
|
Volume/pages
|
|
|
|
10
(2019)
, 15 p.
| |
|
Article Reference
|
|
|
|
119
| |
|
ISI
|
|
|
|
000460446900004
| |
|
Pubmed ID
|
|
|
|
30741928
| |
|
Medium
|
|
|
|
E-only publicatie
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|
Full text (open access)
|
|
|
|
| |
|