Abstract 165: Angiotensinogen M235T Modifies the Relationship between PAI-1 and Renal Blood Flow in Caucasian Hypertensive Individuals

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Qaiser Shafiq ◽  
Bei Sun ◽  
Jonathan S Williams
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Renin Angiotensin System ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Cardiovascular Damage ◽  
Genotype Frequencies ◽  
Hardy Weinberg Equilibrium ◽  
The Relationship ◽  
Pai 1

Studies have reported an association of angiotensinogen (AGT) gene polymorphisms with hypertension and renal blood flow (RBF). The T allele of rs699 (AGT 235T) is associated with increased levels of angiotensinogen and reduced RBF. Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of the fibrinolytic pathway. Elevated PAI-1 is associated with increased renin-angiotensin system (RAS) activity and cardiovascular damage. We hypothesized that hypertensive individuals with the TT genotype of AGT 235 would display higher levels of PAI-1. We further hypothesized an inverse relationship would be observed between PAI-1 and RBF, and that the strength of this correlation would be dependent on genotype status. A total of 159 Caucasian hypertensive participants (mean age 49.3y, BMI 27.6) had data available for AGT235, PAI-1 and RBF from the HyperPATH study. RBF was measured by para-aminohippurate clearance method while on a liberal salt diet (>200 mmol Na/day for 1 week). Genotype frequencies were in Hardy-Weinberg Equilibrium (MM 41/MT 94/TT 24). Multivariate regression demonstrated the TT genotype was associated with higher PAI-1 levels compared with MT + MM (41.0±8.1 v. 26.9±7.1ng/ml, p=0.005). Genotype status modified the relationship between PAI-1 and RBF whereby only the TT genotype showed a significant correlation after adjusting for age, BMI and BP (TT pr2=0.22, Beta= -1.66 p=0.001 v. MT+MM pr2=0.05, Beta= -0.82, p=0.21). AGT 235T is associated with elevated PAI-1 and influences the relationship between PAI-1 and RBF in Caucasian hypertensives. This provides mechanistic clues to explain the genetic underpinnings involving AGT polymorphisms and hypertension.

scholarly journals Spironolactone Abolishes the Relationship between Aldosterone and Plasminogen Activator Inhibitor-1 in Humans

2002 ◽  
Vol 87 (2) ◽  
pp. 448-452 ◽  
Author(s):  
Pairunyar Sawathiparnich ◽  
Sandeep Kumar ◽  
Douglas E. Vaughan ◽  
Nancy J. Brown
Keyword(s):  
Angiotensin Ii ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type Plasminogen Activator ◽  
Serum Aldosterone ◽  
The Relationship ◽  
Activator Inhibitor ◽  
Pai 1

Recent studies have defined a link between the renin-angiotensin-aldosterone system and fibrinolysis. The present study tests the hypothesis that endogenous aldosterone regulates plasminogen activator inhibitor-1 (PAI-1) production in humans. Hemodynamic parameters, PAI-1 and tissue-type plasminogen activator (t-PA) antigen, potassium, PRA, angiotensin II, and aldosterone were measured in nine male hypertensive subjects after a 3-wk washout, after 2 wk of hydrochlorothiazide (HCTZ; 25 mg plus 20 mmol KCl/d), and after 2 wk of spironolactone (100 mg/d plus KCl placebo). Spironolactone (P = 0.04), but not HCTZ (P = 0.57 vs. baseline; P = 0.1 vs. spironolactone), significantly lowered systolic blood pressure. Angiotensin II increased from baseline during both HCTZ (P = 0.02) and spironolactone (P = 0.02 vs. baseline; P = 0.19 vs. HCTZ) treatments. Although both HCTZ (P = 0.004) and spironolactone (P < 0.001 vs. baseline) increased aldosterone, the effect was greater with spironolactone (P < 0.001 vs. HCTZ). HCTZ increased PAI-1 antigen (P = 0.02), but did not alter t-PA antigen. In contrast, there was no effect of spironolactone on PAI-1 antigen (P = 0.28), whereas t-PA antigen was increased (P = 0.01). There was a significant correlation between PAI-1 antigen and serum aldosterone during both baseline and HCTZ study days (r2 = 0.57; P = 0.0003); however, treatment with spironolactone abolished this correlation (r2 = 0.13; P = 0.33). This study provides evidence that endogenous aldosterone influences PAI-1 production in humans.

Inverse relationship between plasminogen activator inhibitor-1 activity and adiponectin in overweight and obese women

2005 ◽  
Vol 94 (12) ◽  
pp. 1190-1195 ◽  
Author(s):  
Ilse Mertens ◽  
Dominique Ballaux ◽  
Tohru Funahashi ◽  
Yuji Matsuzawa ◽  
Marc Van der Planken ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Plasminogen Activator Inhibitor ◽  
Obese Women ◽  
Plasminogen Activator Inhibitor 1 ◽  
The Difference ◽  
Hs Crp ◽  
Visceral Adipose ◽  
The Relationship ◽  
Activator Inhibitor ◽  
Pai 1

SummaryAdipose tissue is an active endocrine organ secreting different adipokines such as plasminogen activator inhibitor-1 (PAI-1) and adiponectin, among many others. In this study, we investigated the association between PAI-1 activity and serum adiponectin levels in a group of 444 overweight and obese women and assessed the interrelationship with visceral adipose tissue (VAT; CT-scan L4-L5), insulin resistance (HOMA-IR), HDL cholesterol (HDL-chol) and inflammation (hs-CRP). PAI-1 was inversely related to adiponectin (r=-0.25, p<0.001; adjusted for age and BMI).After adjustment for age, VAT, HOMA-IR and hs-CRP, the relationship remained significant (r=-0.15; p=0.001), but disappeared after additional adjustment for HDL-chol (r=-0.09; p=0.067). Subjects were divided in two groups according to the median levels of adiponectin or PAI-1 levels. PAI-1 activity (19.1±11.4 vs. 15.8±8.6 AU/ml; p=0.003) and adiponectin levels (9.8±4.6 vs. 8.4±4.0 μg/ml; p<0.001) were significantly higher in the low adiponectin/PAI-1 groups. The difference in PAI-1 remained significant after adjustment for age and BMI (p=0.001), became borderline significant after adjustment for age and VAT (p=0.052), and disappeared after adjustment for age and HOMA-IR (p=0.116) or age and HDL-chol (p=0.443).The difference in adiponectin levels remained significant after adjustment for age, VAT, HOMA-IR and hs-CRP (p=0.006), but disappeared after additional adjustment for HDL-chol (p=0.089). Further analyses suggest a contribution of HOMA-IR and/or HDL-chol in the relationship between PAI-1 and adiponectin. HDL-chol was found to be the only factor independently determining both factors. In conclusion, in overweight and obese women, PAI-1 activity was inversely related to serum adiponectin, independent of visceral adipose tissue.

The Prognostic Value of Vascular Endothelial Growth Factor, Urokinase Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Node-Negative Breast Cancer

2004 ◽  
Vol 19 (4) ◽  
pp. 282-288 ◽  
Author(s):  
S. Meo ◽  
R. Dittadi ◽  
L. Peloso ◽  
M. Gion
Keyword(s):  
Breast Cancer ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Vascular Endothelial ◽  
Plasminogen Activator Inhibitor 1 ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Endothelial Growth Factor ◽  
The Relationship ◽  
Pai 1

The vascular endothelial growth factor (VEGF) and the plasminogen activator system play an essential role in solid tumor angiogenesis and in tumor invasion and metastasis. In the present study we investigated the relationship between patient outcome and levels of VEGF, urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in tumor cytosols of 196 node-negative primary invasive breast cancer patients who did not receive any adjuvant therapy. The median follow-up was 65 months. VEGF, uPA and PAI-1 were measured by commercially available enzyme-linked immunosorbent assays. Cox's univariate analysis showed that pT (p=0.0007), uPA (p=0.0156) and PAI-1 (p=0.0015) had a significant impact on relapse-free survival, whereas VEGF did not have any prognostic value (p=0.18). Bivariate analysis showed significant interactions between uPA and PAI-1 (p=0.0035) and between VEGF and PAI-1 (p=0.006). Our study confirms that uPA and PAI-1 cytosol levels can be considered as prognostic factors for relapse-free survival in node-negative breast cancer. Moreover, the interaction between VEGF and PAI-1 warrants further investigation into the relationship between the biomarkers of angiogenesis and those of the protease cascade.

scholarly journals Family-Based Analysis of -675 4G/5G Polymorphism in the PAI-1 Gene in Chinese Polycystic Ovary Syndrome

2021 ◽  
Author(s):  
Li Ge ◽  
Cui Xiao Song ◽  
Sha Dong Wang ◽  
Li Li ◽  
Mei Dong Ma ◽  
...  
Keyword(s):  
Nuclear Family ◽  
Polycystic Ovary ◽  
Direct Sequencing ◽  
Statistical Significance ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Family Based ◽  
The Relationship ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Background: Insulin resistance (IR) is one of the main pathophysiology of PCOS. Previous studies have shown that 4G/5G polymorphism in promoter region of plasminogen activator inhibitor-1 gene(PAI-1) can affect insulin sensitivity by elevating the level and activity of plasma PAI-1, involved in the formation of IR. In order to elucidate the relationship between 4G/5G polymorphism of PAI-1 gene and PCOS, we used transmission disequilibrium test (TDT) to study the nuclear family of PCOS. Purpose: This study used family-based analysis of TDT to determine whether an association exists between 4G/5G polymorphism of PAI-1 gene and PCOS and in Han Chinese in order to identify PAI-1 gene as a genetic susceptibility factor for PCOS. Methods: Eight hundred and fifty-five participants consisting of 285 trios (mother, father and offspring with PCOS) were recruited from the Center for Reproductive Medicine, Shandong University, from July 2007 to August 2014. 4G/5G polymorphism of PAI-1 gene was genotyped using direct sequencing protocol and TDT was used to analyze the association between PAI-1 gene and PCOS. Results: Though the 5G allele in PAI-1 gene was overtransmitted in families, no statistical significance existed and there was no association between PAI-1 gene and PCOS. The levels of FINS, HOMA-IR and TG were significantly different between obese and lean PCOS and the parents.Conclusion: No significant evidence of association or linkage was found between 4G/5G polymorphism of PAI-1 gene and PCOS, indicating that PAI-1 gene was unlikely to play a major role in the etiology of PCOS in our sample.

scholarly journals Immunoreactivity of Plasminogen Activator Inhibitor 1 and Its Correlation with Dysmenorrhea and Lesional Fibrosis in Adenomyosis

2021 ◽  
Author(s):  
Bingxin Yang ◽  
Nihao Gu ◽  
Shu Shi ◽  
Chen Zhang ◽  
Lan Chen ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tumor Metastasis ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Eutopic Endometrium ◽  
Vas Scores ◽  
The Relationship ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
Ectopic Endometrium

AbstractAdenomyosis is associated with dysmenorrhea, infertility, and lesional fibrosis. The pathogenesis of adenomyosis is still unclear. Plasminogen activator inhibitor 1 (PAI-1) plays important roles in pathological activities like tumor metastasis and endometriosis. Our objective was to investigate the expression and localization of PAI-1 in eutopic and ectopic endometrium with adenomyosis and in endometrium without adenomyosis. We also sought to determine the relationship between PAI-1 immunoreactivity and the severity of dysmenorrhea and the extent of lesional fibrosis in adenomyosis. PAI-1 expression was significantly higher in the ectopic endometrium of patients with adenomyosis than in both the eutopic endometrium of patients with adenomyosis and the endometrium of controls. Ectopic PAI-1 expression correlated positively with dysmenorrhea visual analog scale (VAS) scores and the extent of lesional fibrosis in adenomyosis. High PAI-1 expression increased the likelihood of moderate to severe dysmenorrhea in adenomyosis. These results suggest that PAI-1 is involved in the adenomyosis-associated dysmenorrhea and lesional fibrosis, which provide a potential target in treating symptomatic adenomyosis.

Relationship between overnight neuroendocrine activity and morning haemostasis in working men

2004 ◽  
Vol 107 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Roland von KÄNEL ◽  
Brigitte M. KUDIELKA ◽  
Adham ABD-el-RAZIK ◽  
Marie-Louise GANDER ◽  
Karl FREY ◽  
...  
Keyword(s):  
Degrees Of Freedom ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Sustained Effects ◽  
Complete Dataset ◽  
Low Cortisol ◽  
The Relationship ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
D Dimer

Sustained effects of SNS (sympathetic nervous system) and HPAA (hypothalamic–pituitary–adrenal axis) hyperactivity on haemostasis have not been investigated. In the present study, we tested for an association of overnight urinary catecholamine and cortisol excretion with morning plasma levels of fibrinogen, PAI-1 (plasminogen activator inhibitor-1) and D-dimer. Participants (639 male industrial employees) with a complete dataset were studied (age, 41±11 years; mean±S.D.). Subjects collected overnight urinary samples and had a fasting morning blood sample drawn. Measurement of urinary adrenaline (epinephrine), noradrenaline (norepinephrine) and cortisol were dichotomized to perform multivariate analyses of (co)variance. Haemostatic parameters were measured by ELISA. Fibrinogen was higher in men with high adrenaline (F7,631=5.68, P=0.018; where the subscripted value represents the degrees of freedom) and high noradrenaline (F7,631=4.19, P=0.041) compared with men with low excretion of the respective hormones. PAI-1 was higher in men with high cortisol than in men with low cortisol (F7,631=4.77, P=0.029). Interaction revealed that subjects with high cortisol/low noradrenaline had higher PAI-1 than subjects with low cortisol/high noradrenaline (P=0.038). Subjects with high adrenaline/high noradrenaline had higher D-dimer than subjects with high adrenaline/low noradrenaline (P=0.029), low adrenaline/high noradrenaline (P=0.022) and low adrenaline/low noradrenaline (not significant). When covariance for several confounders of haemostatic function was determined, the main effect of adrenaline on fibrinogen and the interaction between adrenaline and noradrenaline for D-dimer maintained significance. Although overnight SNS hyperactivity was associated independently with morning hypercoagulability, the relationship between the activity of HPAA and haemostasis was mediated by traditional cardiovascular risk factors.

Abstract 12338: Production of Plasminogen Activator Inhibitor-1 in Infarcted Lesion was Associated With Coronary Endothelial Vasomotor Dysfunction and Progressive Dysfunction of Left Ventricle in Patients With Acute Myocardial Infarction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Takuya Shimizu ◽  
Manabu Uematsu ◽  
Toru Yoshizaki ◽  
Jun-ei Obata ◽  
Takamitsu Nakamura ◽  
...  
Keyword(s):  
Blood Flow ◽  
Plasminogen Activator ◽  
Coronary Blood Flow ◽  
Inverse Correlation ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Infarcted Myocardium ◽  
Flow Response ◽  
Activator Inhibitor ◽  
Pai 1

Experimental studies showed that plasminogen activator inhibitor-1 (PAI-1) is abundantly expressed in the infarcted myocardium and that the increased PAI-1 expression causes an impairment of fibrinolysis in the coronary vascular beds and left ventricular (LV) adverse remodeling after acute myocardial infarction (AMI). However, little is known in humans. Thus, this study examined whether PAI-1 produced in the infarcted lesion may contribute to coronary endothelial dysfunction and LV dysfunction in patients with AMI. Methods: Plasma levels of PAI-1 activity and tissue-plasminogen activator (tPA) protein were measured by ELISA in plasma obtained from aortic root (AO), anterior interventricular vein (AIV), and peripheral vein (PV) in 41 patients with a first AMI due to occlusion of a proximal segment of the LAD at 6 months (M) after MI. Coronary blood flow responses in the LAD to intracoronary infusion of acetylcholine (ACh, 50 μg/min) were measured by an intracoronary flow wire technique 6M after MI. Left ventriculography was repeated twice, 2 weeks (2W) and 6M after MI. Results: The trans-myocardial gradient of PAI-1 from AO to AIV (0.14 ± 0.15 ng/mL), reflecting a production/release of PAI-1 from the infarcted lesion, had an inverse correlation with coronary blood flow response to ACh (r = -0.43 , p = 0.02). The trans-myocardial gradient of PAI-1 had an inverse correlation with the % changes in LV regional motion in the LAD territory from 2W to 6M after MI (r = -0.37, p = 0.02). PAI-1 level in the PV and the trans-myocardial gradient of tPA had no significant correlation with the coronary blood flow response to ACh and the LV regional motion. The trans-myocardial gradient in PAI-1 level was lower in patients taking than not taking angiotensin II receptor blocker (ARB) (n = 22, -0.15 ± 0.19 ng/mL vs. n = 19, 0.48 ± 0.21 ng/mL, respectively, p = 0.03). Conclusions: PAI-1 produced in the infarcted myocardium and released into the coronary circulation was associated with endothelial dysfunction in resistance vessels of the infarct-related coronary arteries and progressive dysfunction of the infarcted region of LV in AMI survivors. ARB might inhibit PAI-1 production in the infarcted myocardium in the chronic phase of MI, which may represent an additional benefit of ARB therapy.

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