| Title: |
Abstract 144: Roles of Aging and Cellular Senescence in Intracranial Aneurysm Rupture |
| Authors: |
Sato, Hiroki; Ikedo, Taichi; Kimura, Tetsuro; Purcell, James; Merrow, Samantha; Sato, Hitomi; Lawton, Michael; Hashimoto, Tomoki |
| Source: |
Stroke ; volume 51, issue Suppl_1 ; ISSN 0039-2499 1524-4628 |
| Publisher Information: |
Ovid Technologies (Wolters Kluwer Health) |
| Publication Year: |
2020 |
| Description: |
Background: Aging is an independent risk factor for the rupture of intracranial aneurysm. One of the hallmarks of aging is chronic tissue inflammation. Sirtuin-1 keeps inflammation in check through the deacetylation of various proteins. It is well known that the levels of Sirtuin-1 in vascular tissues decrease with aging, resulting in chronic vascular inflammation. Age-dependent decrease in Sirtuin-1 may explain the link between aging and increased risk for aneurysmal rupture. Hypothesis: Reduction of Sirtuin-1 promotes aneurysmal rupture by inducing sustained aneurysmal wall inflammation. Methods: First, we assessed the levels of Sirtuin-1 expression in intracranial aneurysm tissues from patients older than 70 y.o. and compared with those from the younger patients (40 to 50 y.o.). Second, using a mouse model, we tested effects of Sirtuin-1 specific activator SRT1720 (15mg/kg/day) and specific inhibitor EX-527 (2.5mg/kg/day) on the development of aneurysmal rupture. In addition, we assessed the mRNA expression of inflammatory cytokines (IL-6, IL-1beta, MCP-1, and MMP-9) in cerebral arteries and aneurysms in mice treated with vehicle, SRT1720, or EX-527. Results: Sirtuin-1 expression levels in intracranial aneurysm tissues from the older patients were lower than those from the younger patients. The pharmacological inhibition of Sirtuin-1 increased rupture rate in mice (vehicle vs. EX-527: 58% vs. 88%, P |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1161/str.51.suppl_1.144 |
| Availability: |
https://doi.org/10.1161/str.51.suppl_1.144; http://journals.lww.com/00007670-202002001-00661 |
| Accession Number: |
edsbas.F8E56D6B |
| Database: |
BASE |