scholarly journals Bone Marrow Plasminogen Activator Inhibitor-1 Influences the Development of Obesity

2006 ◽  
Vol 281 (43) ◽  
pp. 32796-32805 ◽  
Author(s):  
Bart M. De Taeye ◽  
Tatiana Novitskaya ◽  
Linda Gleaves ◽  
Joseph W. Covington ◽  
Douglas E. Vaughan
Keyword(s):  
Bone Marrow ◽  
Plasminogen Activator ◽  
Visceral Fat ◽  
Primary Source ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Diet Induced Obesity ◽  
Activator Inhibitor ◽  
Pai 1

Plasma levels of plasminogen activator inhibitor-1 (PAI-1) are elevated in obesity and correlate with body mass index. The increase in PAI-1 associated with obesity likely contributes to increased cardiovascular risk and may predict the development of type 2 diabetes mellitus. Although adipocytes are capable of synthesizing PAI-1, the bulk of evidence indicates that cells residing in the stromal fraction of visceral fat are the primary source of PAI-1. We hypothesized that bone marrow-derived PAI-1, e.g. derived from macrophages located in visceral fat, contributes to the development of diet-induced obesity. To test this hypothesis, male C57BL/6 wild-type mice and C57BL/6 PAI-1 deficient mice were transplanted with either PAI-1-/-, PAI-1+/-, or PAI-1+/+ bone marrow. The transplanted animals were subsequently fed a high fat diet for 24 weeks. Our findings show that only the complete absence of PAI-1 protects from the development of diet-induced obesity, whereas the absence of bone marrow-derived PAI-1 protects against expansion of the visceral fat mass. Remarkably, there is a link between the PAI-1 levels, the degree of inflammation in adipose tissue, and the development of obesity. Based on these findings we suggest that bone marrow-derived PAI-1 has an effect on the development of obesity through its effect on inflammation.

scholarly journals Plasminogen Activator Inhibitor-1 Confirms the Diagnosis of Hepatic Veno-Occlusive Disease in Patients With Hyperbilirubinemia After Bone Marrow Transplantation

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 2184-2188 ◽  
Author(s):  
Christoph Salat ◽  
Ernst Holler ◽  
Hans-Jochem Kolb ◽  
Brigitte Reinhardt ◽  
Rudolf Pihusch ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Plasminogen Activator ◽  
Marrow Transplantation ◽  
Hepatic Injury ◽  
Plasminogen Activator Inhibitor ◽  
Occlusive Disease ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

AbstractHepatic veno-occlusive disease (VOD) is a frequent and severe complication after bone marrow transplantation (BMT). We previously have described plasminogen activator inhibitor-1 (PAI-1) as a possible marker of VOD. To confirm the significance of this finding, we now determined PAI-1 levels in 31 of 186 consecutive patients undergoing BMT who developed hyperbilirubinemia greater than 3 mg/dL for various reasons. Diagnoses were made by clinical criteria and confirmed by biopsy in 23 of 31 patients. They included VOD (n = 7), acute graft-versus-host disease (GVHD) of the liver (n = 7), and other hepatic injury (n = 17). PAI-1 (mean ± SD) was significantly (P < .001) elevated in patients with VOD (321.6 ± 161.2 ng/mL) as compared with patients with GVHD (22.8 ± 8.4 ng/mL) or other hepatic damage (32.8 ± 30.8 ng/mL) at the timepoint of bilirubin increase. At the peak bilirubin concentration, the corresponding PAI-1 levels were 426.1 ± 230.0 ng/mL in patients with VOD, 41.0 ± 20.6 ng/mL in patients with GVHD, and 44.6 ± 32.9 ng/mL in patients with other hepatic injury (P < .001 VOD v GVHD/other hepatic injury). Our results underline the relevance of PAI-1 in the differential diagnosis of hyperbilirubinemia after BMT and its significance as a sensitive and specific marker of severe VOD.

scholarly journals Gender difference in plasminogen activator inhibitor-1 activity in patients with type 2 diabetes with and without albuminuria, a matched case-control study

2019 ◽  
Vol 9 (7) ◽  
pp. 484
Author(s):  
Mehrnaz Imani ◽  
Soghra Rabizadeh ◽  
Manouchehr Nakhjavani ◽  
Payam Hashemi ◽  
Shaghayegh Pezeshki ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Matched Case ◽  
Matched Case Control Study ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
Control Study

Background: Women with type 2 diabetes are more susceptible to coagulopathy disorders and endothelial dysfunction. One possible explanation is the effects of different sex hormones in inflammatory conditions. Increased plasminogen activator inhibitor-1 (PAI-1) activity has been observed as a possible predisposing factor for coagulopathy disorders and endothelial dysfunction. However, the effect of gender on PAI-1 in patients with type 2 diabetes (T2D) and albuminuria has not been studied sufficiently.Objectives: In this study, we examined whether changes of PAI-1 activity according to the albuminuria state in patients with type 2 diabetes are different in males and females.Materials and Methods: A matched case-control study was performed among participants with T2D, as 38 microalbuminuric patients were matched with 38 normoalbuminuric patients who were similar in age and body mass index (BMI). PAI-1 activity was compared between the two groups with and without gender stratification.Results: PAI-1 activity in microalbuminuric women was higher in comparison to that of the normoalbuminuric controls (P-value < 0.05). There was no significant difference in PAI-1 activity between macroalbuminuric and normoalbuminuric men. In women with type 2 diabetes and albuminuria, PAI-1 activity was independently and significantly associated with urinary albumin excretion.Conclusions: Gender differences in PAI-1 activity, seen in the early stages of diabetic nephropathy, are a possible explanation for the higher incidence of vasculopathy in women with type 2 diabetesKeywords: plasminogen activator inhibitor-1; coagulopathy; microalbuminuria; type 2 diabetes; gender

scholarly journals Effect of Plasminogen Activator Inhibitor-1 and Tissue Plasminogen Activator Polymorphisms on Susceptibility to Type 2 Diabetes in Malaysian Subjects

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Zaid Al-Hamodi ◽  
Riyadh Saif-Ali ◽  
Ikram S. Ismail ◽  
Khaled A. Ahmed ◽  
Sekaran Muniandy
Keyword(s):  
Type 2 Diabetes ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Additive Models ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Plasminogen ◽  
Alu Repeat ◽  
Activator Inhibitor ◽  
Pai 1

Elevated activity of plasminogen activator inhibitor-1 (PAI-1) and decreased tissue plasminogen activator (tPA) activity are considered to be important risk factors for type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). The aim of this study was to investigate the association of the PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms with T2DM in Malaysian subjects. Serum insulin, coronary risk panel, plasma glucose, and PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms were studied in 303 T2DM subjects (227 with MetS and 76 without MetS) and 131 normal subjects without diabetes and MetS. Statistical analysis showed that the dominant and additive models of PAI-1 4G/5G polymorphism showed a weak association with T2DM without MetS (OR=2.35,P=0.045;OR=1.67,P=0.058). On the other hand, the recessive model of the tPA Alu-repeat I/D polymorphism showed an association with T2DM with MetS (OR=3.32,P=0.013) whereas the dominant and additive models of the tPA Alu-repeat I/D polymorphism were not associated with T2DM either with or without MetS.

scholarly journals Down-regulation of Plasminogen Activator Inhibitor 1 Expression Promotes Myocardial Neovascularization by Bone Marrow Progenitors

2004 ◽  
Vol 200 (12) ◽  
pp. 1657-1666 ◽  
Author(s):  
Guosheng Xiang ◽  
Michael D. Schuster ◽  
Tetsunori Seki ◽  
Alfred A. Kocher ◽  
Shawdee Eshghi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Down Regulation ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Mrna And Protein Expression ◽  
Activator Inhibitor ◽  
Pai 1

Human adult bone marrow–derived endothelial progenitors, or angioblasts, induce neovascularization of infarcted myocardium via mechanisms involving both cell surface urokinase-type plasminogen activator, and interactions between β integrins and tissue vitronectin. Because each of these processes is regulated by plasminogen activator inhibitor (PAI)-1, we selectively down-regulated PAI-1 mRNA in the adult heart to examine the effects on postinfarct neovascularization and myocardial function. Sequence-specific catalytic DNA enzymes inhibited rat PAI-1 mRNA and protein expression in peri-infarct endothelium within 48 h of administration, and maintained down-regulation for at least 2 wk. PAI-1 inhibition enhanced vitronectin-dependent transendothelial migration of human bone marrow–derived CD34+ cells, and resulted in a striking augmentation of angioblast-dependent neovascularization. Development of large, thin-walled vessels at the peri-infarct region was accompanied by induction of proliferation and regeneration of endogenous cardiomyocytes and functional cardiac recovery. These results identify a causal relationship between elevated PAI-1 levels and poor outcome in patients with myocardial infarction through mechanisms that directly inhibit bone marrow–dependent neovascularization. Strategies that reduce myocardial PAI-1 expression appear capable of enhancing cardiac neovascularization, regeneration, and functional recovery after ischemic insult.

scholarly journals Bone marrow mesenchymal stem cell-derived exosomes promote plasminogen activator inhibitor 1 expression in vascular cells in the local microenvironment during rabbit osteonecrosis of the femoral head

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Lu Li ◽  
Yikai Wang ◽  
Xiaobing Yu ◽  
Yongming Bao ◽  
Lijia An ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Femoral Head ◽  
Plasminogen Activator ◽  
Vascular Endothelial Cells ◽  
Thrombus Formation ◽  
Plasminogen Activator Inhibitor ◽  
Vascular Cells ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Background Nontraumatic osteonecrosis of the femoral head (NONFH) is a highly disabling orthopedic disease in young individuals. Plasminogen activator inhibitor 1 (PAI-1) has been reported to be positively associated with NONFH. We aimed to investigate the dysregulating PAI-1 in bone marrow mesenchymal stem cells (BMMSCs) and vascular cells in rabbit steroid-induced NONFH. Methods To verify the hypothesis that BMMSCs could promote thrombus formation in a paracrine manner, we collected exosomes from glucocorticoid-treated BMMSCs (GB-Exo) to determine their regulatory effects on vascular cells. microRNA sequencing was conducted to find potential regulators in GB-Exo. Utilizing gain-of-function and knockdown approaches, we testified the regulatory effect of microRNA in exosomes. Results The expression of PAI-1 was significantly increased in the local microenvironment of the femoral head in the ONFH model. GB-Exo promoted PAI-1 expression in vascular smooth muscle cells and vascular endothelial cells. We also revealed that miR-451-5p in GB-Exo plays a crucial role for the elevated PAI-1. Moreover, we identified miR-133b-3p and tested its role as a potential inhibitor of PAI-1. Conclusions This study provided considerable evidence for BMMSC exosomal miR-mediated upregulation of the fibrinolytic regulator PAI-1 in vascular cells. The disruption of coagulation and low fibrinolysis in the femoral head will eventually lead to a disturbance in the microcirculation of NONFH. We believe that our findings could be of great significance for guiding clinical trials in the future.

Sign in / Sign up

Export Citation Format

Share Document