LIMITED RESOURCES EARLY IN DEVELOPMENT ARE ASSOCIATED WITH HYPERTENSION LATER IN LIFE VIA CEREBRAL PROINFLAMMATORY CYTOKINE IL-17

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dc.creatorBurkes, Allisonen_US
dc.creatorCastillo, Angieen_US
dc.creatorSmith, Savannaen_US
dc.creatorSmith, Jonnaen_US
dc.creatorJones, Kylieen_US
dc.creatorCunningham, Marken_US
dc.creator.orcid0000-0003-0302-9389 (Burkes, Allison)
dc.date.accessioned2024-04-18T12:59:04Z
dc.date.available2024-04-18T12:59:04Z
dc.date.issued2024-03-21en_US
dc.description.abstractBACKGROUND: Poverty is pervasive and impacts nearly 17%of children in the U.S. While it is established that adverse childhood experiences (ACEs)such as poverty are associated with hypertension later in life, the mechanisms of this trend remain unclear. The limited bed and nesting (LBN) model simulates poverty in rodents by reducing available bedding by 80% for dams to create a nest for their offspring. The impact of inflammation on hypertension across the lifespan is unknown and is the focus of this study. Specifically, we evaluated 4-week and 17-week offspring to investigate the relationship of early-life stress and inflammation. METHOD: Timed pregnant Sprague Dawley dams gave birth naturally and their pups were weaned for 3 weeks. Postnatal days 2-9, dams and their pups were exposed to normal bedding (CON) or the LBN treatment. Offspring were divided by age, sex, and experimental status:at4weeks {LBN males (n=6), LBN females (n=3), CON males (n=5), CON females(n=5)} and at 17 weeks{ LBN males (n=5), LBN females (n=5), CON males (n=6) and CON females (n=6)}. On day 10, all rats were returned to normal bedding. At 4/17 weeks, offspring brain samples were harvested and analyzed via colorimetric assay to assess proinflammatory cytokineinterleukin-17 (IL-17). Carotid catheterizations were performed on 17-weekoffspring and blood pressures were measured. RESULTS: At 4 weeks, we found a trending difference between combined male and female LBN and CON groups(495.1 ±83.3 vs 291.1 ±64.8pg/mL/mg Protein; p=0.07,ns). Male offspring with LBN treatment had a significant increase in IL-17 concentration compared to CON males (964.3 ±108.5 vs 424.0 ±86.1; p<0.01). At 17 weeks, there was no longer a trending difference between LBN and CON groups with sexes combined, but there was a significant difference between male and female offspring with LBN and CON groups combined (7761 ±1005 vs 4511 ±901pg/mL/mg Protein; p<0.05). Although not significant, LBN Males had an upward trend of IL-17 compared to CON Males, while females showed no differences. Additionally, LBN Males had an upward trend in IL-17 compared to females exposed to LBN (9294 ±1279 vs 4198 ±1595pg/mL/mg Protein; p=0.08,ns). Blood pressure readings at sixteen weeks revealed LBN males have a significant increase in BP compared to CON males(128.17±3.93 vs 110.72±3.93 mmHg, p<0.05)and females showed no change(ns). CONCLUSION: Elevated cerebral IL-17 in male offspring suggests an increased inflammatory response to LBN treatment compared to females who showed no change. Accordingly, male sex may be a risk factor for high inflammatory responses to stress, like poverty. The differences in cytokine expression between males and females suggests that IL-17 contributes to hypertension experienced by LBN males later in life. More research is needed to understand the timeline of physiologic responses to ACEs and to investigate opportunities to intercept the inflammation response described in this study and literature. Future research should continue to develop an understanding of sex impacts on ACEs-related stress to refine treatment recommendations in the future.en_US
dc.description.sponsorshipThis research was supported by start-up funds and the American Heart Association Early Career Development Award [AHA 18CDA34110264 (Cunningham)] and the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health Award [5R25HL007786-29(Jones)].en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12503/32753
dc.language.isoen
dc.titleLIMITED RESOURCES EARLY IN DEVELOPMENT ARE ASSOCIATED WITH HYPERTENSION LATER IN LIFE VIA CEREBRAL PROINFLAMMATORY CYTOKINE IL-17en_US
dc.typeposteren_US
dc.type.materialtexten_US

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