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

IF 3.4 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
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
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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.

纤溶酶原激活物抑制剂-1(PAI-1)的增加及其与早期生活压力下健康年轻人代谢风险的关系
目的我们旨在描述早期生活压力(ELS)、代谢综合征(MetS)和纤溶系统的主要抑制剂纤溶酶原激活物抑制剂-1(PAI-1)之间的相互作用。我们还研究了 ELS、体育锻炼和 PAI-1 之间研究不足的交叉点。方法我们从社区招募了 18-40 岁的健康年轻人(200 人;68% 为女性)。患有 ELS 的参与者(人数=118)曾在童年时期遭受过虐待,其中大多数人(人数=92)在童年时期还曾失去过父母。对照组参与者(82 人)没有童年虐待史或失去父母的经历。参与者目前没有心脏代谢或血栓性疾病。使用 Bio-Plex Pro 人类糖尿病面板(Bio-Rad 实验室)对空腹血浆样本进行代谢风险标志物和总 PAI-1 评估。根据腰围身高比、收缩压和舒张压、甘油三酯、总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇、空腹血浆葡萄糖和血红蛋白 A1c 的平均标准化 z 值计算出综合代谢风险 z 值(MetS 风险)。通过增加循环 PAI-1 水平,ELS 与成年后较高的 MetS Z 评分相关(平均因果中介效应 [ACME]= 0.07,p = 0.036)。ELS 也通过更高的 MetS Z 分数与 PAI-1 水平的增加有关(ACME = 0.02,p < 0.001)。ELS和运动对PAI-1水平有明显的交互影响(p = 0.03),因此在ELS患者中,每天进行较多的运动与较低的PAI-1水平有关。在 ELS 患者中,运动与降低 PAI-1 水平有关,这为早期干预提供了潜在的方向。
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来源期刊
Psychoneuroendocrinology
Psychoneuroendocrinology 医学-精神病学
CiteScore
7.40
自引率
8.10%
发文量
268
审稿时长
66 days
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.
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