Chronic unpredictable stress changes left ventricular geometry and activation of the inflammasome

Autor: Amelia Churillo, Lisa Freeburg, Kyle Stegmann, James Doster, Noelle Frambes, Alexia Crockett, Fernanda Priviero, Fiona Hollis, Susan Wood, Clinton Webb, Michael Ryan, Francis Spinale
Rok vydání: 2023
Předmět:
Zdroj: Physiology. 38
ISSN: 1548-9221
1548-9213
DOI: 10.1152/physiol.2023.38.s1.5733103
Popis: Background: Psychosocial stress, particularly chronic unpredictable stress (CUS) has been identified as a risk factor for cardiovascular disease, but the effects of CUS on left ventricle (LV) function, geometry and systemic hemodynamics remains unclear. Moreover, whether and to what degree CUS activates intracellular formation of the inflammasome, including the NOD-LRR pyrin containing protein 3 (NLRP3) remains unknown. Accordingly, the central hypothesis of this project was that in a murine model of CUS, shifts in LV geometry and systemic hemodynamics would occur and be associated with the induction of NLRP3. Methods and Results: Mice (C57BL/6, 10wks of age, equal sex, n=16) were subjected to CUS for 4 weeks which entailed daily random stressors including tilted cage, wet bedding, and overnight light. Referent age and sex matched non CUS mice served as controls (n=16). LV function was assessed by high fidelity ultrasound and blood pressure measurements by tail cuff for both referent control and CUS mice. The changes in ambient heart rate (HR), LV end-systolic volume (LVEDV), and systolic blood pressure (SBP) were expressed as a function of referent control. All results are reported as mean ± SEM. While LV ejection fraction was equivalent between CUS and control groups (70 ± 3 vs. 67 ± 3%, respectively, p=0.48), HR trended higher (4.5 ± 3.1%, p=0.08), LVEDV was lower (-11 ± 5%, p=0.03) and SBP was elevated (12.1 ± 4.9%, p=0.04) - all indicative of heightened sympathetic tone. LV myocardial NLRP3 (rtPCR) was increased (1.47 ± 0.22 fold change, p=0.04) with CUS as was IL-1β (1.43 ± 0.20 fold change, p=0.05), a downstream cytokine activated by NLRP3. Conclusion: CUS, in and of itself, shifts LV geometry, causes mild hypertension and induction of the myocardial inflammasome- all of which would exacerbate/contribute to cardiovascular disease. This work was supported in part by National Institutes of Health grant R01HL130972-01A1 (F.G.S.), R01HL5949 (F.G.S.), RO1DK132948 (C.W. & F.P.), R01 MH129798 (SKW) and P20GM109091 (F.H.) as well as a Merit Award from the Veterans Health Administration, BX000168-10A1 (F.G.S.), BX005320 (F.G.S.), BX002604 (M.J.R.), and VISN7 RDA (F.H.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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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