Association of circulating factor seven activating protease (FSAP) and of oral Omega-3 fatty acids supplements with clinical outcome in patients with atrial fibrillation: the OMEGA-AF study.

Factor VII Activating Protease (FSAP) activates factor VII (FVII) as well as pro-urokinase (uPA). Our goal was to evaluate the relation between plasma levels of FSAP and clinical instability in atrial fibrillation (AF) and possible effects of oral omega-3 fatty acids (FA) supplements. 101 patients with persistent AF were analyzed in the OMEGA-AF Study. Plasma FSAP levels were measured at baseline and after 12 weeks of treatment with omega-3 FA. The median FSAP antigen concentration, in contrast to FSAP activity, was higher in patients with persistent AF. The maintenance of SR after successful cardioversion (CV) did not lead to a normalization of FSAP concentration. Supplementation with omega-3 FA but not placebo significantly reduced elevated FSAP concentration. Furthermore, elevated FSAP levels did not indicate a significantly increased risk of recurrence of AF after electrical CV or cardiovascular clinical events during 1 year of follow-up. Plasma FSAP concentration was increased in patients with AF and may be involved in the pathogenesis of this condition. The possible effects of omega-3 FA on clinical AF potential could be linked with modulation of circulating FSAP levels.

Factor seven activating protease (FSAP) expression in human placenta and its role in trophoblast migration.

OBJECTIVES: Factor seven activating protease (FSAP) is a plasma serine protease known to play a critical role in hemostasis and remodeling processes: FSAP levels increase markedly during normal pregnancy. In order to define the role of FSAP in vascular pathophysiology in pregnant women and particularly in the placenta, we performed this study (i) to evaluate the FSAP expression in human placenta and (ii) to identify the role of FSAP in human trophoblast migration. STUDY DESIGN: FSAP expression in placental tissues was analyzed by using immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). To determine whether FSAP plays any role in trophoblast migration, we used human trophoblast cells in transwell migration assays. RESULTS: Immunohistochemistry showed that FSAP protein was expressed by syncytiotrophoblast and in the cytoplasma of invasive extravillous trophoblasts (EVT) within the maternal decidua (DC) in implantation sites of human first trimester placenta. Furthermore, FSAP mRNA and protein decreased with gestational age (p<0.05, 1st vs 3rd trimester). FSAP (10µg/ml) had a significant stimulatory effect on the migration of human trophoblast cells. This effect was abolished by addition of aprotinin to block the enzymatic activity of FSAP. CONCLUSIONS: The high expression level of FSAP in the placenta supports a relevant role of this protease in trophoblast migration and vascular remodeling, identifies a new concept of coagulation/fibrinolysis at the feto-maternal interface and may be essential for the maintenance of pregnancy.

Circulating factor VII activating protease (FSAP) is associated with clinical outcome in acute coronary syndrome.

BACKGROUND: Factor VII activating protease (FSAP) is a circulating serine protease strongly expressed in unstable plaques and may serve as a marker of plaque destabilization. The aim of this study was to examine the relation between plasma concentrations of FSAP and clinical instability and outcome in coronary artery disease (CAD). METHODS AND RESULTS: Circulating FSAP concentration and activity, as well as FSAP mRNA expression in monocytes, were measured in 231 sequential patients who underwent coronary angiography because of stable angina pectoris (n=50), unstable angina pectoris (n=43), or acute myocardial infarction (n=87). FSAP activity, but not FSAP antigen concentration, was elevated in patients with CAD compared with a control group. Elevated FSAP activity (≥1.035 plasma equivalent units [PEU]/ml) indicated a significantly increased risk of death or non-fatal myocardial infarction during 1 year of follow-up as compared with patients with low activity of FSAP (odds ratio 1.895 [95% confidence interval 1.093-3.283]; P=0.023). Furthermore, there were no significant changes in the FSAP expression in monocytes from CAD and control subjects in the basal state but there were differences after stimulation with proinflammatory factors. CONCLUSIONS: Plasma FSAP activity was significantly increased in patients with acute coronary syndrome and may be involved in the pathogenesis of these conditions. High levels of FSAP activity were predictive of adverse events during follow-up, suggesting its potential role in risk stratification and clinical management of CAD patients.

[Investigations concerning the threshold value between endogenous and exogenous GHB (liquid ecstasy)]. / Untersuchungen zum Grenzwert zwischen endogener und exogener gamma-hydroxybuttersäure (GHB/Liquid Ecstasy).

The article describes critical investigations concerning the threshold value between endogenous and exogenous concentrations of gamma-hydroxybutyric acid (GHB/"liquid ecstasy") in human blood. The values of GHB in the blood samples of 50 blood donors and 50 postmortem cases were measured with a validated gas-chromatographic/mass-spectrometric procedure according to the guidelines of the GTFCh (Society of Toxicological and Forensic Chemistry). GHB-concentrations were found to range between 0.11 and 1.56 mg/L (mean value 0.54 mg/L/standard deviation 0.37 mg/L/coefficient of variation 68.4 %) in the donors' blood, and between 2.2 and 116 mg/L (mean value 32.4 mg/L/standard deviation 25.6 mg/L/coefficient of variation 79 %) in the postmortem samples, respectively.