Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Göteborg, Sweden.
Department of Public Health and Community Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
PLoS One. 2022 Aug 31;17(8):e0267833. doi: 10.1371/journal.pone.0267833. eCollection 2022.
The main inhibitor of the fibrinolytic system, Plasminogen Activator Inhibitor -1 (PAI-1), irreversibly binds tissue-type Plasminogen Activator (t-PA) and thereby inhibits the protective action of tPA against thrombus formation. Elevated levels of plasma PAI-1 are associated with an increased risk of cardiovascular events and are observed in subjects with type 2 diabetes (T2D) and obesity. Platelets contain the majority of PAI-1 present in blood and exhibit the ability to synthesis active PAI-1. Diabetic platelets are known to be hyper-reactive and larger in size; however, whether these features affect their contribution to the elevated levels of plasma PAI-1 in T2D is not established.
To characterize the PAI-1 antigen content and the mRNA expression in platelets from T2D subjects compared to obese and lean control subjects, in order to elucidate the role of platelet PAI-1 in T2D.
Nine subjects with T2D and obesity were recruited from Primary Care Centers together with 15 healthy control subjects (8 lean subjects and 7 with obesity). PAI-1 antigen levels in plasma, serum and platelets were determined by ELISA, and PAI-1 mRNA expression was analyzed by qPCR.
There was no significant difference in PAI-1 mRNA expression or PAI-1 antigen in platelets in T2D subject in comparison to obese and lean control subjects. An elevated level of plasma PAI-1 was seen in both T2D and obese subjects. PAI-1 gene expression was significantly higher in both obese groups compared to lean.
Similar levels of protein and mRNA expression of PAI-1 in platelets from T2D, obese and lean subjects indicate a limited role of platelets for the elevated plasma PAI-1 levels. However, an increased synthesis rate of mRNA transcripts in platelets from T2D and an increased release of PAI-1 could also result in similar mRNA and protein levels. Hence, synthesis and release rates of PAI-1 from platelets in T2D and obesity need to be investigated to further elucidate the role of platelets in obesity and T2D.
纤维蛋白溶解系统的主要抑制剂，纤溶酶原激活物抑制剂-1（PAI-1），不可逆地结合组织型纤溶酶原激活物（t-PA），从而抑制 tPA 对血栓形成的保护作用。血浆 PAI-1 水平升高与心血管事件风险增加相关，并且在 2 型糖尿病（T2D）和肥胖患者中观察到。血小板含有血液中存在的大部分 PAI-1，并具有合成活性 PAI-1 的能力。已知糖尿病血小板反应过度且体积较大；然而，这些特征是否会影响其对 T2D 中升高的血浆 PAI-1 水平的贡献尚不清楚。
与肥胖和正常体重对照组相比，确定 T2D 患者血小板中的 PAI-1 抗原含量和 mRNA 表达情况，以阐明血小板 PAI-1 在 T2D 中的作用。
从初级保健中心招募了 9 名患有 T2D 和肥胖症的患者，并招募了 15 名健康对照者（8 名正常体重对照者和 7 名肥胖对照者）。通过 ELISA 测定血浆、血清和血小板中的 PAI-1 抗原水平，并通过 qPCR 分析 PAI-1 mRNA 表达。
与肥胖和正常体重对照组相比，T2D 患者血小板中的 PAI-1 mRNA 表达或 PAI-1 抗原无显著差异。T2D 和肥胖患者均出现血浆 PAI-1 水平升高。与正常体重组相比，肥胖组的 PAI-1 基因表达均显著升高。
T2D、肥胖和正常体重患者血小板中的 PAI-1 蛋白和 mRNA 表达水平相似，表明血小板对升高的血浆 PAI-1 水平的作用有限。然而，T2D 和肥胖患者血小板中的 PAI-1 mRNA 转录物合成率增加以及 PAI-1 的释放增加也可能导致相似的 mRNA 和蛋白水平。因此，需要研究 T2D 和肥胖患者血小板中 PAI-1 的合成和释放率，以进一步阐明血小板在肥胖和 T2D 中的作用。
