Increased plasminogen activator inhibitor-1 (PAI-1) and its associations with metabolic risk in healthy young adults with early life stress.

Autor: Kudinova AY; Department of Pediatrics, Hasbro Children's Hospital and Bradley Hospital, RI, USA; Warren Alpert Medical School, Brown University, Providence, RI, USA., Kulak MJ; Warren Alpert Medical School, Brown University, Providence, RI, USA; Initiative on Stress, Trauma, and Resilience (STAR), Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI, USA. Electronic address: meghan_kulak@brown.edu., Daniels TE; Initiative on Stress, Trauma, and Resilience (STAR), Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI, USA; Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA., Angeles WLL; Department of Pediatrics, Hasbro Children's Hospital and Bradley Hospital, RI, USA; Warren Alpert Medical School, Brown University, Providence, RI, USA., de la Monte S; Department of Pathology, Alpert Medical School of Brown University, Providence, RI, USA; fProvidence VA Medical Center, Providence, RI, USA; Rhode Island Hospital, Providence, RI, USA., Mathis KJ; Initiative on Stress, Trauma, and Resilience (STAR), Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI, USA; The Miriam Hospital, Center for Behavioral and Preventive Medicine, USA., Beck QM; Initiative on Stress, Trauma, and Resilience (STAR), Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI, USA; Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA., Laumann LE; Initiative on Stress, Trauma, and Resilience (STAR), Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI, USA; Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA., Tyrka AR; Initiative on Stress, Trauma, and Resilience (STAR), Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI, USA; Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA.
Jazyk: angličtina
Zdroj: Psychoneuroendocrinology [Psychoneuroendocrinology] 2024 Aug; Vol. 166, pp. 107071. Date of Electronic Publication: 2024 May 08.
DOI: 10.1016/j.psyneuen.2024.107071
Abstrakt: Objectives: We aimed to characterize the interplay between early life stress (ELS), metabolic syndrome (MetS), and plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system implicated in cardiometabolic diseases. We also examined the understudied intersection of ELS, physical activity and PAI-1.
Methods: Healthy young adults ages 18-40 (N=200; 68% female) were recruited from the community. Participants with ELS (N=118) experienced childhood maltreatment, and the majority (n=92) also experienced childhood parental loss. Control participants (N=82) had no history of childhood maltreatment or parental loss. Participants had no current cardiometabolic or thrombotic conditions. Fasting plasma samples were assessed for markers of metabolic risk and total PAI-1 using the Bio-Plex Pro Human Diabetes Panel (Bio-Rad Laboratories). A composite metabolic risk z-score (MetS risk) was computed from the mean standardized z-scores of waist-to-height ratio, systolic and diastolic blood pressure, triglycerides, total cholesterol, LDL and HLD cholesterol, fasting plasma glucose, and hemoglobin A1c.
Results: We found that a history of ELS was linked to both higher PAI-1 levels and a higher MetS risk score. ELS was associated with a higher MetS Z-score in adulthood via increased circulating PAI-1 levels (Average Causal Mediation Effect [ACME]= 0.07, p = 0.036). ELS was also linked to increased PAI-1 levels via greater MetS z-scores (ACME = 0.02, p < 0.001). There was a significant interaction effect of ELS and exercise on PAI-1 levels (p = 0.03), such that engaging in higher levels of daily exercise was linked to lower PAI-1 levels in individuals with ELS.
Conclusion: Healthy young adults with ELS have elevated PAI-1 levels and metabolic risk scores. Among individuals with ELS, exercise is linked to lower PAI-1 levels, suggesting a potential direction for early intervention.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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