Factor Seven Activating Protease » Clinical Studies

FSAP is elavated in pregnancy and in women using OCs

jreinartz — Fri, 16 Apr 2010 10:13:20 +0000

Parahuleva et al. analyzed whether pregnancy or the use of oral contraceptives (OCs) influences circulating FSAP levels. FSAP levels and activity was measured in plasma samples obtained at different gestation stages from healthy pregnant women, from non-pregnant, pre-menopausal women who currently use OCs, and who did not use OCs.

Plasma FSAP antigen and activity level was significantly higher in late pregnancy than in non-pregnant women. FSAP levels remained elevated after delivery. Plasma FSAP levels in women using OCs was also significantly elevated compared to the control group. Ex vivo experiments demonstrated enhanced FSAP expression in monocytes isolated from women using OCs. In vitro experiments showed that FSAP mRNA levels were strongly induced by estradiol in monocytes but not in hepatocytes.

The authors conclude that hormonal status critically influences the expression of FSAP in pregnancy and in women using OCs. Hormonal influences could be observed in monocytes in vivo and ex-vivo but not in hepatocytes indicating cell-specific regulation.

Title:
Factor Seven Activating Protease (FSAP) levels during normal pregnancy and in women using oral contraceptives

Authors and Source:
Parahuleva MS et al. Thromb Res. 2010 Apr 8. [Epub ahead of print]

Hormon therapy increases FSAP antigen and activiy

jreinartz — Tue, 30 Mar 2010 10:01:41 +0000

Recent studies indicate that FSAP may play roles in the development and expression of atherosclerosis and that FSAP can be involved in the precipitation of coronary heart disease. It was demonstrated, that hormone therapy (HT) has a protective role in coronary heart disease (CHD) in younger postmenopausal women, whereas hormone therapy contributes to coronary heart disease in older women.

The authors explored the potential influence of various hormone therapy regimens on plasma measures of FSAP antigen and activity in postmenopausal women (n= 139) treated for 1 year with different hormone therapy formulations or no hormone therapy.

In conclusion, hormone therapy increases FSAP antigen levels and the scu-PA activating properties of FSAP, suggesting that FSAP may contribute to the CVD-protective effect of hormone therapy observed in younger, postmenopausal women.

Title:
Hormone therapy affects plasma measures of factor VII-activating protease in younger postmenopausal women

Authors and Source:
Sidelmann JJ et al. Climacteric. 2010 Mar 12. [Epub ahead of print]

Effect of oral contraceptives on FSAP

jreinartz — Mon, 02 Nov 2009 09:38:47 +0000

Oral contraceptives (OCs) affect plasma levels of haemostatic factors and the use of OC is a risk factor for development of cardiovascular disease. This study addressed the effect of OCs on FSAP in human blood.

Women were analysed that took oral contraceptives with different estrogen and progestin dosage. Marburg I variant, FSAP antigen and FSAP activity was measured at the start and after 6 cycles of OC. Marburg I was found to be present in 49 (8.4%) of the women, in all three treatment groups (P=0.44). Marburg I was associated with significantly reduced levels of FSAP (P<0.001). OC use increased the median plasma concentration of FSAP antigen by 25% and FSAP activity by 58% (P<0.001). The relative increase in FSAP activity was significantly higher in women carrying the wild type genotype (63%) than in women carrying the Marburg I variant (50%) (P=0.01). The increase in FSAP was independent of the estrogen dosage and progestin (P>0.1).

In conclusion, OCs increased FSAP in plasma independent of the estrogen dosage and the progestin component but with less significance in women carrying Marburg I genotype than in women with the wild type genotype.

Authors and Source
JJ Sidelmann, SO Skouby, C Kluft, U Winkler, F Vitzthum, H Schwarz, J JespersenPoster presentation ISTH 2009: OC-MO-090

Titel
The effect of monophasic oral contraceptive regimens on factor VII-activating protease – a randomized multicentre study

Factor VII-Activating Protease (FSAP) in atherosclerotic plaques

admin — Sun, 24 May 2009 20:18:48 +0000

FSAP was studied at the protein level (immuno-histochemistry) and the mRNA level (PCR) in atherosclerotic lesions obtained by directional coronary atheroectomy. Higher levels of FSAP mRNA (p<0,001) as well as FSAP antigen (p<0,005) were observed in patients with acute coronary syndromes compared to patients with stable angina pectoris. FSAP was also found to be co-localized with the macrophage-rich shoulder of the plaques. In vitro experiments indicated that monocyte-derived macrophages can express FSAP. Parahuleva and his colleagues concluded that FSAP may play a role in plaque destabilization.

Title:
Factor Seven Activating Protease (FSAP) expression in human monocytes and accumulation in unstable coronary atherosclerotic plaques.

Authors and Source:
Parahuleva et al. Atherosclerosis. 2008 Jan;196(1):164-171.

Factor VII-Activating Protease Marburg I variant and carotid stenosis

admin — Sun, 24 May 2009 20:11:58 +0000

Willeit and colleagues analysed the impact of FSAP polymorphism on the evolution and progression of carotid stenosis. They used an ultrasound model of atherosclerosis progression which can differentiate early from advanced stages of vessel disease. 810 men and women between 40 and 79 years (from the so-called “Bruneck” study”) were studied. No correlation was found between FSAP-MI and early atherogenesis, but FSAP-MI appeared as a strong and independent risk predictor of incident/progressive carotid stenosis (multivariate odds ratio [95 %CI], 6,6 [1,.6 to 27.7]). The authors conclude, that the Marburg 1 polymorphism of FSAP (FSAP G511E) “… is a significant risk predictor for the evolution and progression of carotid stenosis.”

Title:
Marburg I polymorphism of factor VII-activating protease: a prominent risk predictor of carotid stenosis.

Authors and Source:
Willeit et al., Circulation. 2003 Feb 11;107(5):667-670.

Factor VII-Activating Protease Marburg I variant and cardiovascular risk

admin — Sun, 24 May 2009 20:06:26 +0000

In their “Northwick Park Heart Study II” Ireland and colleagues addressed the risk for coronary disease in a prospective study of cardiovascular disorders. They found an interactive effect upon risk between the FSAP G511E allele and elevated levels of cholesterol, triglyeride, or fibrinogen. This was taken to conclude that “…the FSAP G511E allele exacerbates atherosclerosis or its clinical sequelae.”

Title:
The factor VII activating protease G511E (Marburg) variant and cardiovascular risk.

Authors and Source:
Ireland et al., Thromb Haemost. 2004 Nov;92(5):986-992.

Factor VII-Activating Protease and Liver Cirrhosis

admin — Sun, 24 May 2009 18:05:17 +0000

Wasmuth and colleagues addressed the fact that genetic factors affect the progression of liver fibrosis in chronic hepatitis C (HCV) infection and they asked whether the Marburg I variant of FSAP (FSAP G511E allele) might play a role. Their findings suggest that the G511E variant is a risk locus for HCV-induced liver fibrosis and cirrhosis. The reason may be the reduced ability of FSAP-MI to down-regulate PDGF-mediated hepatic stellate proliferation (see Roderfeld et al. below, link). The authors conclude that FSAP G511E “… might be useful for risk stratification in patients with HCV-infection”.

Title:
The marburg I variant (G534E) of the factor VII-activating protease determines liver fibrosis in hepatitis C infection by reduced proteolysis of platelet-derived growth factor BB.

Authors and Source:
Wasmuth et al. Hepatology. 2009 Mar;49(3):775-780.