Plasma Plasminogen Activator Inhibitor Type 1 Research Articles

PAI-1 as a critical factor in the resolution of sepsis and acute kidney injury in old age.

Elevated plasma levels of plasminogen activator inhibitor type 1 (PAI-1) are documented in patients with sepsis and levels positively correlate with disease severity and mortality. Our prior work demonstrated that PAI-1 in plasma is positively associated with acute kidney injury (AKI) in septic patients and mice. The objective of this study was to determine if PAI-1 is causally related to AKI and worse sepsis outcomes using a clinically-relevant and age-appropriate murine model of sepsis. Sepsis was induced by cecal slurry (CS)-injection to wild-type (WT, C57BL/6) and PAI-1 knockout (KO) mice at young (5-9months) and old (18-22months) age. Survival was monitored for at least 10 days or mice were euthanized for tissue collection at 24 or 48h post-insult. Contrary to our expectation, PAI-1 KO mice at old age were significantly more sensitive to CS-induced sepsis compared to WT mice (24% vs. 65% survival, p = 0.0037). In comparison, loss of PAI-1 at young age had negligible effects on sepsis survival (86% vs. 88% survival, p = 0.8106) highlighting the importance of age as a biological variable. Injury to the kidney was the most apparent pathological consequence and occurred earlier in aged PAI-1 KO mice. Coagulation markers were unaffected by loss of PAI-1, suggesting thrombosis-independent mechanisms for PAI-1-mediated protection. In summary, although high PAI-1 levels are clinically associated with worse sepsis outcomes, loss of PAI-1 rendered mice more susceptible to kidney injury and death in a CS-induced model of sepsis using aged mice. These results implicate PAI-1 as a critical factor in the resolution of sepsis in old age.

The 4G/5G Polymorphism of Plasminogen Activator Inhibitor Type 1 is a Predictor of Moderate-to-Severe Thyroid Eye Disease.

IntroductionThyroid eye disease (TED) is an autoimmune disease of the orbits. Once developed, complete cure is rare. Plasminogen activator inhibitor type 1 (PAI-1) contributes to remodeling of connective tissue and has a central role in the pathogenesis of TED. We aimed to test if the 4G/5G polymorphism of PAI-1 is a predictor of the development of moderate-to-severe TED.MethodsA total of 185 patients with Graves’ disease, 87 of them with TED, 98 without TED, as well as 201 healthy controls, were studied. Genomic DNA was isolated from peripheral blood samples. The 4G/5G polymorphism of the PAI-1 gene was analyzed by allele-specific PCR, and the distribution of genotypes was calculated in each group. Plasma PAI-1 and thyroid hormone levels were measured by ELISA and ECLIA, respectively.ResultsThe 4G/4G genotype was associated with the development of moderate-to-severe TED (OR = 2.54; 95% CI: 1.26–5.14; p < 0.01). The 4G/5G polymorphism of PAI-1 was not a predictor of plasma PAI-1 levels.ConclusionThe 4G/4G genotype of PAI-1 is a risk factor for the development of moderate-to-severe TED. Patients with Graves’ disease who harbor this genotype may be candidates for special attention towards the development of TED.

Effect of a Recombinant Dimeric Tumor Necrosis Factor Receptor on Inflammatory Responses to Intravenous Endotoxin in Normal Humans

AbstractTo determine the role of tumor necrosis factor (TNF ) in lipopolysaccharide (LPS)-induced inflammation, 12 healthy subjects received an intravenous injection with LPS (2 ng/kg) preceded by infusion of either a recombinant human dimeric TNF receptor type II-IgG fusion protein (TNFR:Fc; 6 mg/m2; n = 6) or vehicle (n = 6) from −30 minutes to directly before LPS injection. LPS elicited a transient increase in plasma TNF activity, peaking after 1.5 hours (219 ± 42 pg/mL; P < .05). Infusion of TNFR:Fc completely neutralized endogenous TNF activity. LPS administration was associated with an early activation of fibrinolysis (plasma concentrations of tissue-type plasminogen activator, plasminogen activator activity, and plasmin-α2 -antiplasmin complexes), followed by inhibition (plasma plasminogen activator inhibitor type I), changes that were completely prevented by TNFR:Fc. By contrast, TNFR:Fc did not influence LPS-induced activation of coagulation (plasma levels of prothrombin fragment F1 + 2 and thrombin-antithrombin III complexes). TNFR:Fc strongly inhibited endothelial cell activation (plasma levels of soluble E-selectin), modestly reduced neutrophil responses (neutrophilia and plasma concentrations of elastase-α1 -antitrypsin complexes and lactoferrin), but did not affect the release of secretory phospholipase A2 or lipopolysaccharide-binding protein (P < .05). Infusion of TNFR:Fc only (without LPS) in another 6 normal subjects did not induce any inflammatory response. These data indicate that TNF is involved in only some inflammatory responses to intravenous LPS in humans.

ПОКАЗНИКИ ДЕЯКИХ КОМПОНЕНТІВ СИСТЕМИ АКТИВАЦІЇ ПЛАЗМІНОГЕНУ ПРИ РАКУ СЕЧОВОГО МІХУРА

Bladder cancer (BC) continues to be a disease with a high mortality rate. Bladder cancer is the sixth for men and seventeenth for women in the incidence of malignancy worldwide. The invasion and metastasis of malignant tumors are caused by a sequence of processes, including loss of cell-cell and / or cell-matrix adhesion, proteolysis, and induction of angiogenesis. Different protease systems are involved in these processes, especially during the invasion and development of metastases. One such protease system is a plasminogen activation system or fibrinolysis system. Changes in the balance of plasminogen activation systems have been investigated in many types of malignancies, and these changes may not only indicate the functioning of this system but may also have prognostic significance. In malignancies, the components of this system are involved in the growth, invasion, and metastasis of tumors, affecting cell migration and angiogenesis. The main, but a well-studied component of the plasminogen activation system is serine proteinase – urokinase-type plasminogen activator (uPA). In contrast to uPA, tissue-type plasminogen activator (tPA) is characterized by a high affinity for fibrin and is involved in thrombolysis. Both types of plasminogen activators are synthesized in tumor tissues: tPA and uPA. The largest player among the inhibitors of fibrinolysis is the plasminogen activator inhibitor type 1 (PAI-1), involved in the pathogenesis of many cardiovascular diseases, as well as in cancer. The purpose of this study was to detect changes in the content of plasminogen activator tissue type tPA and PAI-1 in the blood plasma of patients with BC at different stages of the disease. The study involved 40 men who were verified with a diagnosis of BC. The content of tPA and PAI-1 in preoperative blood plasma was determined by enzyme immunoassay in ELISA modification. In our study, changes in the tPA and PAI-1 content of the blood plasma at different stages were identified, which can characterize tumor growth and invasion and can supplement existing disease information.

Recognition of Plasminogen Activator Inhibitor Type 1 as the Primary Regulator of Fibrinolysis.

The fibrinolytic system consists of a balance between rates of plasminogen activation and fibrin degradation, both of which are finely regulated by spatio-temporal mechanisms. Three distinct inhibitors of the fibrinolytic system that differently regulate these two steps are plasminogen activator inhibitor type-1 (PAI-1), α2-antiplasmin, and thrombin activatable fibrinolysis inhibitor (TAFI). In this review, we focus on the mechanisms by which PAI-1 governs total fibrinolytic activity to provide its essential role in many hemostatic disorders, including fibrinolytic shutdown after trauma. PAI-1 is a member of the serine protease inhibitor (SERPIN) superfamily and inhibits the protease activities of plasminogen activators (PAs) by forming complexes with PAs, thereby regulating fibrinolysis. The major PA in the vasculature is tissue-type PA (tPA) which is secreted from vascular endothelial cells (VECs) as an active enzyme and is retained on the surface of VECs. PAI-1, existing in molar excess to tPA in plasma, regulates the amount of free active tPA in plasma and on the surface of VECs by forming a tPA-PAI-1 complex. Thus, high plasma levels of PAI-1 are directly related to attenuated fibrinolysis and increased risk for thrombosis. Since plasma PAI-1 levels are highly elevated under a variety of pathological conditions, including infection and inflammation, the fibrinolytic potential in plasma and on VECs is readily suppressed to induce fibrinolytic shutdown. A congenital deficiency of PAI-1 in humans, in turn, leads to life-threatening bleeding. These considerations support the contention that PAI-1 is the primary regulator of the initial step of fibrinolysis and governs total fibrinolytic activity.

Changes in the plasma level of plasminogen activator inhibitor-1 in patients with cranio-cerebral trauma depending on body weight and PAI-1 -675 4G/5G gene polymorphism

Purpose. To study the association between the plasma level of plasminogen activator inhibitor type-1 (PAI-1) and both body weight and PAI-1 -675 4G/5G gene polymorphism in patients with cranio-cerebral trauma (CCT) over the treatment course. Materials and methods. The hemostasis system state was analyzed in 200 patients with CCT by studying the association between the plasma level of PAI-1 and both body weight and -675 4G/5G polymorphism of the PAI-1 gene. For statistical processing of the obtained study results, a licensed version of the SPSS STATISTICA 17 program was used. K-means cluster analysis was also performed; the Euclidean distance was used as the distance measure. Results. Clustering of patients was performed depending on the plasma PAI-1 content on days 1, 7 and 14 after trauma. All patients were distributed into 3 clusters. Thus, the first cluster included patients with the average PAI-1 concentration within the normal range during the study. The second cluster included patients who presented significantly increased PAI-1 concentration at the time of an injury, which tended to decrease rapidly and almost normalized by day 14. The third cluster consisted of patients with significantly increased plasma concentration of PAI-1 following an injury with the tendency to remain at a high level for 14 days. Due to statistical processing of the study results, an association between an increase in PAI-1 level and both the 4G/4G, 4G/5G genotypes and overweight or obesity in patients was found. Increased levels of PAI-1 were observed in overweight or obese patients with the 4G/4G and 4G/5G genotypes over the course of treatment. Conclusions. The association between both overweight and -675 4G/5G polymorphism of the PAI-1 gene and plasma level of plasminogen activator inhibitor type-1 in patients with traumatic brain injury has been proven.

Longitudinal assessment of D-dimer and plasminogen activator inhibitor type-1 plasma levels in pregnant women with risk factors for preeclampsia

ABSTRACTObjective: Investigating D-Dimer/D-Di and plasminogen activator inhibitor type-1/PAI-1 levels throughout gestation in women with preeclampsia/PE risk factors.Methods: D-Di and PAI-1 plasma levels were determined in 28 women at 12–19, 20–29, 30–34 and 35–40 weeks of gestation.Results: D-Di was lower at 12–19 weeks and higher at 30–34 weeks in women who developed PE versus who did not develop it. D-Di increased throughout gestation in both groups, peaking earlier in pregnant women who developed PE versus who did not develop it. PA1-1 increased across gestation, but it didn’t differ between groups.Conclusion: D-Di was able to discriminate these groups of women at 12–19 and 30–34 weeks of gestation.

Plasminogen Activator Inhibitor Type 1 in Blood at Onset of Chemotherapy Unfavorably Affects Survival in Primary Ovarian Cancer.

Plasminogen activator inhibitor type 1 (PAI-1) belongs to the family of the plasminogen activator system. PAI-1 stimulates fibrinolysis and also promotes tumor progression. The aim of this study was to evaluate the prognostic value of blood plasma PAI-1 content in patients with epithelial ovarian cancer who start the first-line chemotherapy. PAI-1 content was measured in the blood of 61 patients with epithelial ovarian cancer at onset of first-line chemotherapy. The patients were further stratified into the low PAI-1 group (≤20ng/mL; 33 patients) and the high PAI-1 group (>20ng/mL; 28 patients). We found that the greater plasma PAI-1 content was associated with a significantly lower probability of a 5-year-long survival compared to that when PAI-I content was lower (45.5% vs. 69.5%, respectively; p=0.04). However, the risk of cancer recurrence within 5years failed to differ appreciably. A multivariate analysis revealed that the lower PAI-1 plasma content was an independent factor of longer overall survival (death risk ratio of 0.36, 95%CI=0.16-0.79; p<0.01). We conclude that PAI-1 is yet another biomarker of survival in patients with ovarian cancer.

PECULIARITIES OF NEPHROPROTECTIVE EFFECT OF SULODEXIDE IN PATIENTS WITH DIABETIC NEPHROPATHY

Introduction. Monocyte chemoattractant protein type 1 (MCP-1) and plasminogen activator inhibitor type 1 (PAI-1) play a key role in inflammation, fibrosis and progression of renal dysfunction. Sulodexide advantages in vascular pathology treatment were proved by clinical trials, however, its efficiency in diabetic nephropathy (DN) was investigated insufficiently.&#x0D; The aim of the present work – to study the influence of sulodexide on clinical and laboratory parametres, MCP-1 and PAI-1 levels in blood plasma of patients with DN.&#x0D; Materials and methods. 76 type 2 diabetic patients with different stages of DN were observed. 44 patients received basic therapy with anti-diabetic drugs and ACE- inhibitors, 32 patients in addition to basic therapy were treated with sulodexide in a daily dose 600 LU. Concentrations of MCP-1 and PAI-1 in blood plasma were determined using immunoassay kits.&#x0D; Results. In patients with DN when compared with healthy controls MCP-1 and RAI-1 levels in blood plasma significantly increased already at initial stages of the disease. Such changes may promote a development of inflammatory and fibrotic processes in kidneys. Progression of the disease was accompanied by more essential growth of MCP-1 and RAI-1 in DN patients with expressed clinical manifestations of kidney injury. Sulodexide treatment in patients with DN resulted in essential decrease of inflammatory and fibrotic markers and had positive effect on urinary protein excretion.&#x0D; Conclusions. Glicosaminoglycans, in particular, sulodexide, is effective in complex treatment of patients with DN.

Inhibitory effect of water extractive components from heshiko and narezushi on plasma PAI-1 activity in rats

The effect of water-extractive components solutions (extracts) from heshiko and narezushi, fermented mackerel products, on plasminogen activator inhibitor type-1 (PAI-1) was investigated in rats. Administration of heshiko and narezushi extracts tended to suppress the increase in both PAI-1 activity and total content associated with high-fat diet administration in rats. PAI-1 activity but not total content showed a relation to plasma triglyceride level and a reverse relation to tPA activity before and after administration of heshiko and narezushi extracts. The extracts directly inhibited PAI-1 activity in vitro, and the inhibitory activity was not lost after alimentary enzyme digestion of the extracts. The PAI-1 inhibitory activity of heshiko extract was tended to be stronger than that of narezushi extract. These results suggest that heshiko and narezushi extracts are closely involved in the promotion of fibrinolytic activity via direct PAI-1 inhibition as well as indirect suppression by decreasing the plasma triglyceride level.

The Selective Sirtuin 1 Activator SRT2104 Reduces Endotoxin-Induced Cytokine Release and Coagulation Activation in Humans.

Sirtuin 1 influences gene expression and other cellular functions through deacetylation of histone and nonhistone proteins. We here sought to determine the effects of a small molecule sirtuin 1 activator, SRT2104, on inflammation and coagulation induced by lipopolysaccharide in humans. A randomized, double-blind, placebo-controlled study. An academic hospital. Twenty-four healthy humans. All subjects received an intravenous injection with lipopolysaccharide. Subjects were randomized to one of three groups (n=8 per group): 1) pretreatment with oral SRT2104 for 7 days (2 g/d), 2) pretreatment with a single SRT2104 dose (2 g), or 3) placebo. SRT2104 attenuated lipopolysaccharide-induced release of the cytokines interleukin-6 (mean peak levels of 58.8% [p<0.05] and 80.9% [p=0.078] after single and repeated SRT2104 administration, respectively, relative to those measured after placebo treatment) and interleukin-8 (mean peak levels of 57.0% [p<0.05 vs placebo] and 77.1% [p<0.05 vs placebo] after single and repeated SRT2104 ingestion, respectively, while not affecting tumor necrosis factor-α and interleukin-10 release). SRT2104 also reduced the lipopolysaccharide-induced acute phase protein response (C-reactive protein). SRT2104 inhibited activation of coagulation, as reflected by lower plasma levels of the prothrombin fragment F1+2 (mean peak levels 57.9% [p<0.05] and 64.2% [p<0.05] after single and repeated SRT2104 administration, respectively, relative to those measured after placebo treatment). Activation of the vascular endothelium (plasma von Willebrand levels) and the fibrinolytic system (plasma tissue-type plasminogen activator and plasminogen activator inhibitor type I) was not influenced by SRT2104. This is the first human study to demonstrate biological anti-inflammatory and anticoagulant responses consistent with the activation of sirtuin 1 by a small molecule.

High-fat diet decreases energy expenditure and expression of genes controlling lipid metabolism, mitochondrial function and skeletal system development in the adipose tissue, along with increased expression of extracellular matrix remodelling- and inflammation-related genes.

The aim of the present study was to identify the genes differentially expressed in the visceral adipose tissue in a well-characterised mouse model of high-fat diet (HFD)-induced obesity. Male C57BL/6J mice (n 20) were fed either HFD (189 % of energy from fat) or low-fat diet (LFD, 42 % of energy from fat) for 16 weeks. HFD-fed mice exhibited obesity, insulin resistance, dyslipidaemia and adipose collagen accumulation, along with higher levels of plasma leptin, resistin and plasminogen activator inhibitor type 1, although there were no significant differences in plasma cytokine levels. Energy intake was similar in the two diet groups owing to lower food intake in the HFD group; however, energy expenditure was also lower in the HFD group than in the LFD group. Microarray analysis revealed that genes related to lipolysis, fatty acid metabolism, mitochondrial energy transduction, oxidation-reduction, insulin sensitivity and skeletal system development were down-regulated in HFD-fed mice, and genes associated with extracellular matrix (ECM) components, ECM remodelling and inflammation were up-regulated. The top ten up- or down-regulated genes include Acsm3, mt-Nd6, Fam13a, Cyp2e1, Rgs1 and Gpnmb, whose roles in the deterioration of obesity-associated adipose tissue are poorly understood. In conclusion, the genes identified here provide new therapeutic opportunities for prevention and treatment of diet-induced obesity.

Effect of vagus nerve stimulation on blood coagulation and fibrinolysis in endotoxemic rats

Objective To evaluate the effect of vagus nerve stimulation on the blood coagulation and fibrinolysis in endotoxemic rats.Methods Ninety-six male Sprague-Dawley rats,weighing 250-280 g,were equally and randomly divided into 4 groups using a random number table:normal saline group (S group) ; lipopolysaccharide (LPS) group; vagus nerve cutting group (VNC group) and vagus nerve stimulation group (VNS group).Endotoxemia was induced by LPS 10 mg/kg injected via the left femoral vein.In group S,normal saline 5 ml/kg was injected via the left femoral vein.In S and LPS groups,the bilateral vagus nerves were only isolated.The bilateral vagus nerves were isolated,ligated and cut immediately after LPS injection in VNC group.The distal end of the vagus nerve was stimulated with direct current (5 V,2 ms,1 Hz) continuously for 20 min starting from the end of LPS injection in group VNS.Six rats were sacrificed before LPS injection (T0) and at 2,4 and 6 h after LPS injection (T1-3) and arterial blood samples were taken for determination of the levels of plasma tumor necrosis factorα (TNF-α),antithrombin (AT),tissue-type plasminogen activator (tPA),plasminogen activator inhibitor type 1 (PAI-1) and D-Dimer.Results Compared with group S,the plasma TNF-α,tPA,PAI-1 and D-Dimer levels were significantly increased,and AT level was decreased after LPS injection in LPS and VNC groups (P ＜ 0.05).Compared with group LPS group,the plasma AT level was significantly decreased,and the plasma PAI-1 level was increased in group VNC,and the plasma TNFα,tPA,PAI-1 and D-Dimer levels were decreased,and the plasma AT level was increased in VNS group (P ＜ 0.05).Conclusion Electrical stimulation of the vagus nerve can improve the blood coagulation and fibinonlysis in endotoxemic rats,and activation of cholinergic anti-inflammatory pathway,inhibition of inflammatory responses and reduction of damage to vascular endothelial cells may be involved in the mechanism. Key words: Vagus Nerve ; Electrical Stimulation ; Endotoxemia ; Blood coagulation

Local and Systemic Expressions of MMP-9, TIMP-1 and PAI-1 in Patients Undergoing Surgery for Clinically Suspected Appendicitis

Background/Aims: To examine, compare and correlate the expressions of matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1) and plasminogen activator inhibitor type 1 (PAI-1) in appendiceal tissue and pre- and postoperative blood samples in patients undergoing surgery for clinically suspected appendicitis. Methods: Fifty-seven patients with complete tissue and blood samples were included and divided into groups of noninflamed appendix/lymphadenitis (n = 7), phlegmonous appendicitis (n = 30), gangrenous appendicitis (n = 11) and perforated appendicitis (n = 9). The protein expressions were assessed with ELISAs. The local expressions of MMP-9, TIMP-1 and PAI-1 were correlated with the systemic expressions at the time of surgery while the systemic individual differences between surgery and recovery were compared. Results: There was a positive correlation between tissue and plasma PAI-1 (p < 0.05). The individual differences for plasma MMP-9 and PAI-1 were statistically nonsignificant, while they were higher for TIMP-1 in patients with perforated appendicitis compared with phlegmonous (p < 0.0001) and gangrenous appendicitis (p < 0.01). Conclusions: Plasma PAI-1 reflected the levels in appendiceal tissue at the time of surgery. Systemic TIMP-1 could have the potential of distinguishing perforated from nonperforated appendicitis.

4G/5G polymorphism modulates PAI-1 circulating levels in obese women

The increase in plasminogen activator inhibitor type 1 (PAI-1) has been described as a risk factor to thrombosis-related diseases. In addition, it has been demonstrated that the variant 4G of polymorphism 4G/5G located in promoter region of PAI-1 gene is associated with higher PAI-1 levels. We investigate the role of this polymorphism on circulating PAI-1 concentration in a population of 57 obese women (23%, 4G/4G; 49%, 4G/5G and 28%, 5G/5G genotypes). Our results demonstrate a genotype-specific modulation on PAI-1 levels in obese women, thus 5G/5G genotype presented significantly lower levels of plasma PAI-1 when compared to 4G/4G group (46 ± 19 ng/mL vs. 63 ± 13 ng/mL, respectively). Our findings indicate that obese carriers of 4G/4G genotype may have increased risk to develop thrombotic diseases.

Effects of Lisinopril, Irbesartan, and Amlodipine on the Thrombogenic Variables in the Early and Late Stages of the Treatment in Hypertensive Patients

Regulation of the fibrinolytic balance between plasminogen activators and inhibitors is modulated by the renin–angiotensin system (RAS). Impaired fibrinolytic function, characterized by increased plasminogen activator inhibitor type 1 (PAI-1) levels and decreased tissue plasminogen activator (t-PA) activity, has been found in patients with hypertension and may account in part for the increased risk of atherosclerosis and its clinical complications in these patients. In this regard, data from the literature indicate that different antihypertensive drugs may vary in their influence on fibrinolysis. Angiotensin-converting enzyme (ACE) inhibitors (ACE-I) have generally been shown to improve the fibrinolytic balance by reducing plasma PAI-1 levels. Calcium-channel blockers (CCB) have been reported to increase t-PA activity, and angiotensin receptor blockers (ARB) seem to be neutral in their effect. In the light of these data, this study aimed to compare the effects of ACE-I, ARB, and CCB on the fibrinolytic system in the early and late stages of the treatment in hypertensive patients. These data that the beneficial effect of RAS inhibition on fibrinolysis related to decrease in Ang II during early period of treatment. Amlodipine may also improve thrombogenic risk related to lowering the effect on increased platelet activation reflected by p-selectin. The greater improvement in the early and late stages of the fibrinolytic balance because of the combined action of RAS inhibition and Ca antagonism represents a further indication to the use of combinations of RAS inhibition (ACE-I or ARB) and CCB in the treatment of hypertension.

Fibronectin, Plasminogen Activator Inhibitor Type 1 (PAI-1) And Uterine Artery Doppler Velocimetry as Markers of Preeclampsia

Objective: The purpose of this study was to examine plasma levels of fibronectin and plasminogen inhibitor type 1 (PAI-1), and alterations in uterine artery (UtA) waveforms throughout normotensive and preeclamptic pregnancies and to analyze its predictive value for the detection of preeclampsia within the second trimester of pregnancy.Material and methods: Blood samples were collected from 102 healthy, nulliparous women between the 24th and 26th gestational week. Preeclampsia developed in 13 patients; 89 normotensive control subjects were matched from the same cohort. Plasma samples were assayed for fibronectin and PAI-1 by enzyme-linked immunosorbent assay. Color pulsed Doppler examinations of UtA were performed after blood sampling. Trends were compared between two groups.Results: Maternal plasma fibronectin and PAI-1 levels and average PI, RI and S/D ratios of patients with preeclampsia were significantly higher (p &lt; 0.05). The best cut-off values for predicting preeclampsia of fibronectin, PAI-1, PI, RI, S/D ratio based on ROC curve analysis were 290 mg/ml, 77.3 ng/ml, 1,0615, 0.605 and 2,59 respectively. The areas under the curve equal to 0.705, 0.753, 0.689, 0.695 and 0.699 for fibronectin, PAI-1 and uterine artery Doppler PI, RI, S/D ratio were determined for the prediction of preeclampsia.Conclusions: Fibronectin, PAI-1 and UtA Doppler are potentially useful predictors of preeclampsia. Maternal plasma PAI-1 combinated with fibronectin had the highest predictive values in our study.

Fibronectin, plasminogen activator inhibitor type 1 (PAI-1) and uterine artery Doppler velocimetry as markers of preeclampsia.

Objective: The purpose of this study was to examine plasma levels of fibronectin and plasminogen inhibitor type 1 (PAI-1), and alterations in uterine artery (UtA) waveforms throughout normotensive and preeclamptic pregnancies and to analyze its predictive value for the detection of preeclampsia within the second trimester of pregnancy. Material and methods: Blood samples were collected from 102 healthy, nulliparous women between the 24th and 26th gestational week. Preeclampsia developed in 13 patients; 89 normotensive control subjects were matched from the same cohort. Plasma samples were assayed for fibronectin and PAI-1 by enzyme-linked immunosorbent assay. Color pulsed Doppler examinations of UtA were performed after blood sampling. Trends were compared between two groups. Results: Maternal plasma fibronectin and PAI-1 levels and average PI, RI and S/D ratios of patients with preeclampsia were significantly higher (p < 0.05). The best cut-off values for predicting preeclampsia of fibronectin, PAI-1, PI, RI, S/D ratio based on ROC curve analysis were 290 mg/ml, 77.3 ng/ml, 1,0615, 0.605 and 2,59 respectively. The areas under the curve equal to 0.705, 0.753, 0.689, 0.695 and 0.699 for fibronectin, PAI-1 and uterine artery Doppler PI, RI, S/D ratio were determined for the prediction of preeclampsia. Conclusions: Fibronectin, PAI-1 and UtA Doppler are potentially useful predictors of preeclampsia. Maternal plasma PAI-1 combinated with fibronectin had the highest predictive values in our study.

Effect of combined angiotensin‐converting enzyme and aldosterone inhibition on plasma plasminogen activator inhibitor type 1 levels in chronic hypertensive patients

A possible link between the renin-angiotensin-aldosterone system (RAAS) and fibrinolysis has recently been suggested. Systemic infusion of angiotensin II results in an increase in plasminogen activator inhibitor type 1 (PAI-1) levels and angiotensin-converting enzyme inhibitors (ACEI) have been shown to decrease PAI-1 levels. Moreover, recent data indicated that plasma aldosterone levels were positively correlated with plasma PAI-1 levels. This study was designed to compare the effects of an ACEI with an ACEI in combination with an aldosterone antagonist on PAI-1 levels in chronic hypertensive patients. Patients were randomized into two groups and were treated with either low salt diet plus fosinopril (group 1, n = 43) or low salt diet plus fosinopril plus spironolactone (group 2, n = 42). Plasma PAI-1, tissue plasminogen activator (tPA) and plasma renin activity (PRA) levels were measured before and after 24 week treatment in both groups. The mean basal PRA levels were similar in both groups. After antihypertensive therapy, the mean PRA increased significantly in both groups (P < 0.005). The mean plasma PAI-1 levels were reduced in both treatment groups (P < 0.005). However, the reduction in group 2 was more pronounced (P < 0.05). Although after the treatment mean plasma levels of PAI-1 significantly reduced in both groups, the reduction of PAI-1 levels was more pronounced in group 2. Although the plasma levels of PAI-1 significantly reduced after treatment in both groups, the reduction of PAI-1 levels was more pronounced in group 2. These data indicated that administration of aldosterone antagonists in combination with ACEI had additional benefit on fibrinolysis in chronic hypertensive patients.

Whole and Refined Grain Intakes Are Related to Inflammatory Protein Concentrations in Human Plasma

Inflammation may play a role in the pathogenesis of cardiovascular disease and type 2 diabetes, and it has been suggested that the protective effects of whole-grain consumption could be mediated by an effect on inflammation, although few studies have examined the relationships between grain intakes and inflammatory protein concentrations. Our objectives in this study were to examine the associations of whole grain and refined grain intake with plasminogen activator inhibitor type 1 (PAI-1), C-reactive protein (CRP), and fibrinogen plasma concentrations. Cross-sectional data from the Insulin Resistance Atherosclerosis Study were used to perform multiple regression analyses using dietary information on whole and refined grain intakes from a FFQ and clinical measures of plasma inflammatory protein concentrations in participants free of type 2 diabetes. After adjustment for demographic, lifestyle, and dietary variables, whole-grain intake was inversely related to log PAI-1 (β = −0.102; SEM = 0.038; P = 0.0077) and log CRP (β = −0.102; SEM = 0.048; P = 0.0340). Adding insulin sensitivity, waist circumference, and 2-h postload glucose to the model attenuated both associations to nonsignificance. Refined grain was positively related to log PAI-1 in the multivariate model (β = 0.076; SEM = 0.034; P = 0.0251) and the relationship remained unchanged by additional adjustment for metabolic variables. Fibrinogen concentrations were not related to whole or refined grain intake. In summary, whole grain intake was inversely related to PAI-1 and CRP plasma concentrations, but these relationships were attenuated by the addition of metabolic variables to the model. Refined grain intake was positively independently related to plasma PAI-1 concentrations.