Functional Stability of Plasminogen Activator Inhibitor-1

Yıldız, Songül Yaşar; Kuru, Pinar; Öner, Ebru Toksoy; Ağırbaşlı, Mehmet

doi:10.1155/2014/858293

Cited by 76 publications

(61 citation statements)

References 132 publications

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“…PAI-1 is known for its role in regulating the balance between the fibrinolytic system and the thrombotic system101147. Previous studies have shown that patients with DM2 have high levels of PAI-1, which acts as an independent thrombotic risk factor1316.…”

Section: Discussionmentioning

confidence: 99%

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Hyperglycaemia-induced reciprocal changes in miR-30c and PAI-1 expression in platelets

Luo

Ren

et al. 2016

Sci Rep

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Type 2 diabetic mellitus (DM2) is associated with accelerated thrombotic complications and is characterized by high levels of plasminogen activator inhibitor-1 (PAI-1). Recent studies show that human platelets have high levels of miR-30c and synthesize considerable active PAI-1. The underlying mechanism of how PAI-1 expression is upregulated in DM2 is poorly understood. We now report that hyperglycaemia-induced repression of miR-30c increases PAI-1 expression and thrombus formation in DM2. Bioinformatic analysis and identification of miRNA targets were assessed using luciferase assays, quantitative real-time PCR and western blots in vitro and in vivo. The changes in miR-30c and PAI-1 levels were identified in platelets from healthy and diabetic individuals. We found that miR-30c directly targeted the 3′ UTR of PAI-1 and negatively regulated its expression. miR-30c was negatively correlated with glucose and HbA1c levels in DM2. In HFD-fed diabetic mice, increasing miR-30c expression by lenti-miR-30c significantly decreased the PAI-1 expression and prolonged the time to occlusion in an arterial thrombosis model. Platelet depletion/reinfusion experiments generating mice with selective ablation of PAI-1 demonstrate a major contribution by platelet-derived PAI-1 in the treatment of lenti-miR-30c to thrombus formation. These results provide important implications regarding the regulation of fibrinolysis by platelet miRNA under diabetic mellitus.

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Section: Discussionmentioning

confidence: 99%

“…PAI-1 acts as the main circulating inhibitor of plasminogen activation in the fibrinolytic system1011. In DM2, elevated levels of PAI-1 lead to impaired fibrinolytic function and have been associated with a greater risk of cardiovascular disease1213.…”

mentioning

confidence: 99%

Hyperglycaemia-induced reciprocal changes in miR-30c and PAI-1 expression in platelets

Luo

Ren

et al. 2016

Sci Rep

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“…Obesity triggers metabolic syndrome, which can lead to atherosclerosis and ischemic heart disease. Increased PAI‐1 levels have been observed in many disease conditions, including obesity . Although visceral fat area was not measured in the present study, blood coagulability was associated with BMI, an indicator of the degree of obesity.…”

Section: Discussionmentioning

confidence: 99%

Relationship between blood coagulability and sense of burden among caregivers of patients with dementia

Hirano

Suzuki

Umegaki

et al. 2019

Geriatrics Gerontology Int

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Aim This study aimed to examine the relationship between blood coagulability and sense of burden among caregivers of patients with senile dementia of the Alzheimer type. Methods A cross‐sectional study was carried out involving healthy older caregivers who lived with their patients with senile dementia of the Alzheimer type. We evaluated the Zarit Burden Interview score, levels of von Willebrand factor antigen, D‐dimer, thrombin–antithrombin III complex, tissue plasminogen activator/plasminogen activator inhibitor type 1 complex, number of chronic diseases, body mass index and number of medications. A linear regression model was used to estimate adjusted associations. Results Thrombin–antithrombin III complex levels were higher in female caregivers than in male caregivers (P = 0.07). Headaches were significantly more frequent in female caregivers than in male caregivers, as assessed by a visual analog scale (P < 0.01). The number of chronic diseases and body mass index were positively associated with levels of tissue plasminogen activator/plasminogen activator inhibitor type 1 complex (P < 0.05). Similarly, the number of medications was positively associated with levels of D‐dimer (P < 0.05). However, the Zarit Burden Interview score was not associated with blood coagulability (P > 0.05). Conclusions The present study found that the number of chronic diseases and body mass index were associated with blood coagulability, and that female caregivers were more prone to headaches and higher blood coagulability than male caregivers. These findings highlight the essential nature of health management during caregiving. The impact of caregiver burden on blood coagulability is likely to differ depending on the long‐term or short‐term psychological stress associated with caregiving conditions. Geriatr Gerontol Int 2019; 19: 804–808.

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“…Like α2‐AP, PAI‐1 is a member of the serpin family . A variety of cells synthesize PAI‐1, including hepatocytes, adipocytes and endothelial cells . The PAI‐1 gene is located on chromosome 7, and its expression can be induced by several factors such as insulin .…”

Section: Methodsmentioning

confidence: 99%

Hemorrhagic disorders of fibrinolysis: a clinical review

Saes

Schols

Heerde³

et al. 2018

Journal of Thrombosis and Haemostasis

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Hyperfibrinolytic bleeding can be caused by a deficiency of one of the inhibitors of fibrinolysis (plasminogen activator inhibitor type 1 [PAI-1] or α2-antiplasmin [α2-AP]), or an excess of one of the activators of fibrinolysis: tissue-type plasminogen activator or urokinase-type plasminogen activator. This review focuses on the clinical implications of these disorders. The bleeding phenotype of fibrinolytic disorders is characterized by delayed bleeding after trauma, surgery and dental procedures. Bleeding in areas of high fibrinolytic activity is also common, such as menorrhagia and epistaxis. Patients with α2-AP deficiency present with the most severe bleeding episodes. Recently, it was discovered that hyperfibrinolytic disorders are associated with a high rate of obstetric complications such as miscarriage and preterm birth, especially in PAI-1 deficient patients. Hyperfibrinolytic disorders are probably underdiagnosed because of lack of knowledge and lack of accurate diagnostic tests. A substantial part of the large group of patients diagnosed as 'bleeding of unknown origin' could actually have a hyperfibrinolytic disorder. In the case of a high index of suspicion (i.e. because of a positive family history, recurrent bleeding or uncommon type of bleeding such as an intramedullary hematoma), further testing should not be withheld because of normal results of standard hemostatic screening assays. Timely diagnosis is important because these disorders can generally be treated well with antifibrinolytic agents.

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Functional Stability of Plasminogen Activator Inhibitor-1

Cited by 76 publications

References 132 publications

Hyperglycaemia-induced reciprocal changes in miR-30c and PAI-1 expression in platelets

Hyperglycaemia-induced reciprocal changes in miR-30c and PAI-1 expression in platelets

Relationship between blood coagulability and sense of burden among caregivers of patients with dementia

Hemorrhagic disorders of fibrinolysis: a clinical review

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