Anastacia Y. Kudinova , Meghan J. Kulak , Teresa E. Daniels , William Lewis-de los Angeles , Suzanne de la Monte , Karen Jennings Mathis , Quincy M. Beck , Laura E. Laumann , Audrey R. Tyrka
{"title":"Increased plasminogen activator inhibitor-1 (PAI-1) and its associations with metabolic risk in healthy young adults with early life stress","authors":"Anastacia Y. Kudinova , Meghan J. Kulak , Teresa E. Daniels , William Lewis-de los Angeles , Suzanne de la Monte , Karen Jennings Mathis , Quincy M. Beck , Laura E. Laumann , Audrey R. Tyrka","doi":"10.1016/j.psyneuen.2024.107071","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><p>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.</p></div><div><h3>Methods</h3><p>Healthy young adults ages 18–40 (<em>N</em>=200; 68% female) were recruited from the community. Participants with ELS (<em>N</em>=118) experienced childhood maltreatment, and the majority (<em>n</em>=92) also experienced childhood parental loss. Control participants (<em>N</em>=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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":20836,"journal":{"name":"Psychoneuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychoneuroendocrinology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S030645302400115X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Psychoneuroendocrinology publishes papers dealing with the interrelated disciplines of psychology, neurobiology, endocrinology, immunology, neurology, and psychiatry, with an emphasis on multidisciplinary studies aiming at integrating these disciplines in terms of either basic research or clinical implications. One of the main goals is to understand how a variety of psychobiological factors interact in the expression of the stress response as it relates to the development and/or maintenance of neuropsychiatric illnesses.