Plasminogen Activator Inhibitor-1

Simon, Daniel I.; Simon, Norman

doi:10.1161/circulationaha.113.006321

Cited by 7 publications

(3 citation statements)

References 25 publications

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“…Tetranectin also enhances plasminogen activation and plasma TNA levels have been inversely associated with coronary artery disease [ 52 ]. Increased levels in AAT and decreased levels in TNA in response to albuminuria point in the same direction, taking in an impairment of the regulation of the anticoagulation system and in agreement with a potential therapeutical intervention over plasminogen activator inhibitor (PAI-1) in hypertensives [ 53 ].…”

Section: Discussionmentioning

confidence: 96%

Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression

González-Calero

Martin‐Lorenzo

Cuesta

et al. 2016

Cardiovasc Diabetol

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BackgroundHypertension is a multi-factorial disease of increasing prevalence and a major risk factor for cardiovascular mortality even in the presence of adequate treatment. Progression of cardiovascular disease (CVD) occurs frequently during chronic renin-angiotensin-system (RAS) suppression, and albuminuria is a marker of CV risk. High prevalence of albuminuria in treated hypertensive patients has been demonstrated, but there are no available markers able to predict evolution. The aim of this study was the identification of novel indicators of albuminuria progression measurable in urine of diabetic and non-diabetic patients.Methods1143 hypertensive patients under chronic treatment were followed for a minimum period of 3 years. Among them, 105 diabetic and non-diabetic patients were selected and classified in three groups according to albuminuria development during follow-up: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Differential urine analysis was performed by 2D gel electrophoresis (2D-DIGE) and further confirmed by liquid chromatography-mass spectrometry. Non-parametric statistical tests were applied.ResultsCD59 glycoprotein and alpha-1 antitrypsin (AAT) resulted already altered in patients developing albuminuria de novo, with a similar response in those with maintained albuminuria. A prospective study in a sub-group of normoalbuminuric patients who were clinically followed up for at least 1 year from urine sampling, revealed CD59 and AAT proteins significantly varied in the urine collected from normoalbuminurics who will negatively progress, serving as predictors of future albuminuria development.ConclusionsCD59 and AAT proteins are significantly altered in hypertensive patients developing albuminuria. Interestingly, CD59 and AAT are able to predict, in normoalbuminuric individuals, who will develop albuminuria in the future, being potential predictors of vascular damage and CV risk. These findings contribute to early identify patients at risk of developing albuminuria even when this classical predictor is still in the normal range, constituting a novel strategy towards a prompt and more efficient therapeutic intervention with better outcome.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0331-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 96%

Urinary alpha-1 antitrypsin and CD59 glycoprotein predict albuminuria development in hypertensive patients under chronic renin-angiotensin system suppression

González-Calero

Martin‐Lorenzo

Cuesta

et al. 2016

Cardiovasc Diabetol

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“…In 2004, Calo et al observed that higher concentrations of aldosterone were instead able to stimulate levels of PAI-1 in all subjects; this effect is probably mediated by MR activation [ 42 ]. In vascular tissue, PAI-1 promotes the accumulation of extracellular matrix and regulates vascular remodeling and perivascular fibrosis [ 43 ], leading to an imbalance in the fibrinolytic system that could lead to thrombotic events such as myocardial infarction or stroke [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Low Cortisone as a Novel Predictor of the Low-Renin Phenotype

Tapia-Castillo,

Carvajal,

Pérez

et al. 2024

Journal of the Endocrine Society

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A large proportion of low-renin hypertensive (LRH) patients correspond to primary aldosteronism. However, some of these subjects have low to normal aldosterone. Since low-renin is driven by excessive mineralocorticoids or glucocorticoids acting on mineralocorticoid receptor (MR), we hypothesize that a low-cortisone condition, associated classically to 11BHSD2 deficiency, is a proxy of chronic MR activation by cortisol, which also can lead to low-renin, elevated blood pressure, renal and vascular alterations. Objective To evaluate low cortisone as a predictor of low-renin activity and its association with parameters of kidney and vascular damage. Design A cross-sectional study was carried out in 206 adult subjects. The subjects were classified according to low renin activity (<1 ng/ml*h) and low-cortisone (<p25th). Results Renin activity was associated with aldosterone (r = 0.36; p < 0.001) and cortisone (r = 0.22; p = 0.001). A binary logistic regression analysis showed that serum cortisone per ug/dl increase predicted the LR phenotype (OR = 0.4 [95% CI, 0.21–0.78]). The ROC curves for cortisone showed an AUC of 0.6 to discriminate subjects with low-renin activity from controls. The low-cortisone subjects showed higher albuminuria and PAI-1 and lower sodium excretion. The association study also showed that urinary cortisone was correlated with blood pressure and serum potassium (p < 0.05). Conclusion This is the first study showing that low-cortisone is a predictor of a low-renin condition. Low-cortisone predicted also surrogate markers of vascular and renal damage. Since the aldosterone to renin ratio is used in the screening of PA, low cortisone values should be considered additionally to avoid false positives in the ARR calculation.

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“…Inhibition of the fibrinolytic system by PAI-1 overexpression, moreover, has been implicated in various pathologies including tissue fibrosis, metabolic disorders and cardiovascular disease (i.e., atherosclerosis, vessel stenosis). A recent report, furthermore, highlights this causative relationship and provides evidence that a small molecule PAI-1 inhibitor (TM5441) confers protection to the development of cardiac hypertrophy, hypertension and periaortic fibrosis in L-NAME-treated mice [ 32 , 33 ].…”

Section: Pai-1 In Vascular Pathologymentioning

confidence: 99%