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• W4360953208 abstract "Mitochondrial dysfunction and inflammation contribute to a myriad of cardiovascular diseases. Deleterious crosstalk of mitochondria and persistent endoplasmic reticulum (ER) stress triggers oxidative stress, which is involved in the development of vascular diseases. This study determined if inhibition of mitochondrial stress reduces aneurysm development in angiotensin II (Ang II)-infused apolipoprotein-E-deficient (ApoE-/- ) mice and its effect on ER stress.The mitochondria-targeted tetrapeptide, Szeto-Schiller 31 (SS31), ameliorated mitochondrial dysfunction and the enhanced expression of ER stress markers triggered by Ang II in ApoE-/- mice, and limited plasmatic and vascular reactive oxygen species (ROS) levels. Interestingly, SS31 improved survival, reduced the incidence and severity of abdominal aortic aneurysm (AAA), and the Ang II-induced increase in aortic diameter as evaluated by ultrasonography, resembling the response triggered by the classic ER stress inhibitors tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyrate (PBA).Disorganization of the extracellular matrix, increased expression of metalloproteinases and pro-inflammatory markers and infiltration of immune cells induced by Ang II in the abdominal aorta were effectively reduced by SS31 and ER inhibitors. Further, C/EBP homologous protein (CHOP) deficiency in ApoE-/- mice attenuated Ang II-mediated increase in vascular diameter and incidence of AAA, suggesting its contribution to the favourable response induced by ER stress inhibition.Our data demonstrate that inhibition of mitochondrial stress by SS31 limits AAA formation and increases survival through a reduction of vascular remodelling, inflammation and ROS, and support that attenuation of ER stress contributes to the favourable response elicited by SS31." @default.
• W4360953208 created "2023-03-26" @default.
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• W4360953208 date "2023-04-25" @default.
• W4360953208 modified "2023-10-18" @default.
• W4360953208 title "Targeting mitochondrial stress with SS31 prevents experimental abdominal aortic aneurysm: crosstalk with ER stress." @default.
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• W4360953208 doi "https://doi.org/10.1111/bph.16077" @default.
• W4360953208 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36964990" @default.
• W4360953208 hasPublicationYear "2023" @default.
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