The short-chain fatty acid acetate improves age-associated vascular endothelial dysfunction

Autor: Nathan Greenberg, Abigail Casso, Alexandra Lindquist, Nicholas VanDongen, Sophia Mahoney, Zachary Clayton, Douglas Seals, Vienna Brunt
Rok vydání: 2023
Předmět:
Zdroj: Physiology. 38
ISSN: 1548-9221
1548-9213
DOI: 10.1152/physiol.2023.38.s1.5726704
Popis: Aging is the primary risk factor for cardiovascular diseases (CVD), the leading cause of death worldwide. Vascular endothelial dysfunction, a key antecedent to CVD, is primarily mediated by excess superoxide-related oxidative stress and decreased nitric oxide (NO) bioavailability. High-fiber diets (H-FIB) are associated with lower CVD-related morbidity/mortality, but adherence to guidelines for recommended dietary fiber intake is poor. Benefits of H-FIB are likely mediated by fermentation of soluble fiber into short-chain fatty acids (SCFAs) in the gut, which may improve endothelial function. Thus, supplementing SCFAs may be a more practical/effective intervention to reduce CVD risk with aging. PURPOSE: To determine if oral supplementation with acetate, the most prevalent SCFA in circulation, reverses vascular endothelial dysfunction in old mice as effectively as a H-FIB. METHODS: Old (O: 24mo) and young (Y: 3mo) male C57BL/6 mice (N=10-17/group) were randomized into 3 groups per age: 1) standard chow (15% total & 2.5% soluble fiber) + normal drinking water (YC/OC); 2) standard chow + 100mM calcium acetate supplemented in drinking water (YA/OA); or 3) H-FIB (20% total & 8% soluble fiber [inulin added to the standard chow]) + normal drinking water (YF/OF). Endothelium-dependent dilation (EDD; ex vivo carotid artery dilation to increasing doses of acetylcholine) and associated mechanisms were assessed following 8 weeks of intervention. RESULTS: Data are mean ± SE. Age-related impairments in peak EDD (YC: 92±1%; OC: 81±2%, p0.8 vs. YC), suggesting that the interventions effects are specific to aging. There were no differences in smooth muscle sensitivity to NO (peak dilation to sodium nitroprusside; OC: 98±1%; OA: 99±0%; OF: 99±0%, p=0.1), indicating that differences in EDD were endothelium-dependent. Instead, these changes were likely NO-mediated, as addition of the endothelial NO synthase inhibitor L-NAME abolished differences in peak EDD (OC: 51±4%; OA: 47±8%; OF: 54±6%, p=0.8). Aortic superoxide production (electron paramagnetic resonance spectroscopy) was lower in old acetate-treated mice (OC: 50±7; OA: 29±3 AU, p=0.04), and tended to be lower in H-FIB mice (OC vs. OF: 33 AU, p=0.18). Incubation with the superoxide scavenger TEMPOL improved peak EDD in OC mice (OC: 81±2%; OC+TEMPOL: 93±2%, p K99/R00 HL151818, F31 HL164004 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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