25-Hydroxycholesterol reduces aortic cellular senescence and stiffness in old mice
| Autor: | Sophia Mahoney, Serban Ciotlos, Mary Darrah, Ravinandan Venkatasubramanian, Matthew Rossman, Judith Campisi, Douglas Seals, Simon Melov, Zachary Clayton |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Physiology. 38 |
| ISSN: | 1548-9221 1548-9213 |
| DOI: | 10.1152/physiol.2023.38.s1.5711505 |
| Popis: | Aortic stiffnessincreases with aging and is an independent risk factor for the development of cardiovascular diseases. Cellular senescence, a state of cell cycle arrest that accumulates in arteries with aging, contributes to age-related aortic stiffening. 25-Hydroxycholesterol (25HC) is a novel senolytic — a compound that eliminates senescent cells by modulating senescent cell anti-apoptotic pathways (SCAPs). However, the senolytic effects of 25HC in the vasculature and its influence on age-related aortic stiffness and associated arterial wall structural remodeling are unknown. Hypothesis: 25HC treatment in old mice treated would favorably modulate the vascular SCAP profile, suppress vascular cell senescence, and reduce aortic stiffness relative to old control mice. Methods & Results. Animals. Two groups (n=10-15/group) of old (24-26mo) female p16-3MR mice were used: 1) untreated control; and 2) 25HC (50 mg/kg/day in 22.5% 2-hydroxypropyl-β-cyclodextrin administered intraperitoneally for 5 consecutive days). SCAPs. Aortic abundance of CRYAB, the therapeutic target of 25HC and a SCAP regulator, was 38% lower in 25HC-treated v. control mice (chemiluminescence units [CU]; PINK4A, a protein that confers cell cycle arrest in senescent cells (CU, P R01 AG055822, K99 HL159241, F31 HL165885 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process. |
| Databáze: | OpenAIRE |
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