Clinical studies on plasma fibronectin and factor XIII; with special reference to hyperlipoproteinemia

Cucuianu, M; Rus, Horea; Cristea, Anca; Niculescu, Florin; Bedeleanu, D; Poruţiu, Dorin; Roman, S

doi:10.1016/0009-8981(85)90210-4

Cited by 12 publications

(7 citation statements)

References 20 publications

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“…A higher plasma fibronectin concentration was found in FCHL patients (541 Ϯ 147 mg/l) than in controls (329 Ϯ 89 mg/l). It was recently reported that fibronectin is elevated in ischemic heart disease and that hypertriglyceridemia especially is associated with plasma fibronectin concentrations (26). We observed remarkable similarities in the pattern of plasma fibronectin levels in four phenotype catagories (i.e., NL, HC, HTG, or CHL) and the pattern of cellular fibronectin secretion in incubations with plasma from either of these catagories.…”

Section: Discussionsupporting

confidence: 63%

Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cells

Greevenbroek

Vermeulen

Bruin

2002

Journal of Lipid Research

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The aim of this study was to evaluate whether soluble factors in plasma of familial combined hyperlipidemia (FCHL) patients affect hepatic protein secretion. Cultured human hepatocytes, i.e., HepG2 cells, were incubated with fasting plasma (20%, v/v, in DMEM) from untreated FCHL patients or normolipidemic controls. Overall protein secretion was 10-15% higher after incubation with FCHL plasma. This was specifically caused by an increase in four secreted proteins, with estimated sizes of 240, 180, 120, and Ͻ 40 kD ( P Ͻ 0.001, P Ͻ 0.006, P Ͻ 0.002, P Ͻ 0.02, respectively). The 240 kD protein in the secretion proteome was identified as fibronectin by mass spectrometry. Plasma fibronectin concentrations were elevated in FCHL patients, confirming biological relevance of these data. Overall protein secretion by HepG2 cells correlated with concentrations of triglycerides ( r ‫؍‬ 0.61, P Ͻ 0.001) in the applied plasma samples. VLDL ؉ IDL isolated from FCHL patients, induced a higher protein secretion than lipoproteins isolated from controls ( P Ͻ 0.001). Remarkably, secretion of apoB, the structural protein of VLDL, was stimulated to a similar extent by FCHL and control plasma. Familial combined hyperlipidemia (FCHL) is a common dyslipidemia with a strong genetic component. The prevalence of FCHL in the population is 1-2% and FCHL is estimated to cause 10-20% of premature coronary heart disease (CHD) (1). Metabolic disturbances in FCHL include overproduction of atherogenic apolipoprotein B (apoB)-containing lipoproteins (i.e., VLDL), delayed clearance of lipoproteins, increased plasma apoB concentrations, increased free fatty acid (FFA) fluxes, and insulin resistance. The molecular mechanism(s) that underlie these metabolic abnormalities are not yet known. It has been suggested that increased plasma FFA fluxes, potentially induced by insulin resistance, may increase hepatic secretion of apoB containing lipoproteins. However, available data on the direct effects of increased FFA fluxes on hepatic apoB production in normal human subjects are limited and apparently conflicting (2, 3). These data do not yet allow defenitive conclusions on the hepatic abnormality in FCHL.The liver plays a central role in the development of atherosclerosis (4). It is an important source of vaso-active compounds as well as atherogenic, apoB containing lipoproteins. Current knowledge on intrahepatic assembly of apoB containing lipoproteins mainly derives from studies in laboratory animals and cells in culture (5). Following intracellular association of lipid with apoB, the precursor lipoproteins fuse with lumenal triglyceride droplets to form mature VLDL that is secreted from the cells (6). The scarce availability of hepatocytes from human FCHL patients renders it not feasible to directly study the role of the liver-specific pathways in FCHL in vitro. It is presently unresolved whether the hepatic hypersecretion of lipoproteins that is observed in FCHL is a process inherent to metabolic abnormalities in the liver, or may be driven by s...

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Section: Discussionsupporting

confidence: 63%

Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cells

Greevenbroek

Vermeulen

Bruin

2002

Journal of Lipid Research

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“…In hyperlipidemic subjects, the fi brin stabilizing factor XIII was found to have increased (24). On the other hand, HCD rats showed an increase in plasma fibrinogen levels with an increase in the activity of a2-plasmin inhibitor that inactivates the plasmin effect to dissolve fibrin clots.…”

Section: Discussionmentioning

confidence: 99%

Correlation between Plasma Fibrinogen and Serum Lipids in Rats with Hyperlipidemia Induced by Cholesterol Free-High Fructose or High Cholesterol Diet.

Okazaki

Zhang

Yoshida

et al. 1994

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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SummaryWe studied the coagulative and fibrinolytic activity in in trinsic or extrinsic hyperlipidemia using 4-week-old male Wistar rats. Intrinsic hyperlipidemia was induced by a cholesterol-free high-fructose diet (HFD) and extrinsic hyperlipidemia, by a high-cholesterol diet (HCD) for 14days. In intrinsic hyperlipidemic rats fed on the HFD, serum lipids were significantly increased as compared with the levels in control rats fed on a standard diet. An apparent increase in plasma fi brinogen level and coagulant factor XIII activity was also observed in HFD rats. In extrinsic hyperlipidemic rats fed on the HCD, significant increases in plasma fibrinogen level compared with that of control rats were found with the increases in serum lipids. Activities of antithrombin III and a2-plasmin inhibitor in HFD-fed rats significantly increased compared with those of control and HFD rats. There was a significant positive correlation between plasma fibrinogen and serum total cholester ol, free cholesterol, or phospholipid in diet-induced hyperlipidemia (p< 0.01). Because of the increase in coagulant XIII activity in HFD-fed rats and the increase in a2-plasmin inhibitor activity in HCD-fed rats, both diet-induced hyperlipidemic rats were shown to have enhanced coagula tive activity compared with the control rats. These results suggest that the HFD as well as the HCD causes a pre-hypercoagulative state due to the increase in plasma fibrinogen level and activities in other coagulative and fi brinolytic factors.

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“…Hyperlipidemic nephrotic patients were also found to present obviously increased plasma levels of factor XIII, fibronectin and fibrinogen (2) as well as raised antiplasmin activity (8,9). Surprisingly, during a preliminary study, dilute blood clot lysis was not prolonged but rather accelerated in such patients.…”

Section: Introductionmentioning

confidence: 93%

“…High levels of plasma factor XIII (1,2) and of the inhibitors of fibrinolysis (3,4) were reported in patients with endogenous hypertriglyceridemia who also displayed an obviously prolonged dilute blood clot lysis time (5). Since fibrin stabilizing plasma factor XIII is known to catalyse the incorporation of a2 plasmin inhibitor (a2 PI) into the fibrin network (6) while inhibition of this transglutaminase by parachlormercuribenzoate (PCMB) or by neohydrin was found to shorten lysis time (5,7) it was considered that the raised plasma levels of factor XIII could at least partially be responsible for the delayed clot lysis noted in hypertrigly ceridemic patients (5).…”

Section: Introductionmentioning

confidence: 99%

Tissue-Type Plasminogen Activator (t-PA) and Dilute Blood Clot Lysis Time in Nephrotic Patients

Cucuianu¹,

Rus²,

Roman³

et al. 1989

Thromb Haemost

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SummaryWhen compared to normal weight normolipidemic control subjects, dilute blood clot lysis time was found to be obviously (p <0.001) prolonged in hypertriglyceridemic patients without proteinuria and slightly (p <0.05) accelerated in hyperlipidemic nephrotic patients in spite of their very high levels of plasma fibrinogen. As a result the ratio plasma fibrinogen (mg/dl) per clot lysis time (minutes) was 1.241 ± 0.08 (X ± SEM) in control subjects, 0.574 ± 0.07 in hypertriglyceridemic patients and 2.69 ± 0.172 in nephrotic patients. This finding suggesting that a larger amount of fibrin is rather readily dispersed from dilute blood clots of nephrotic patients was associated with higher levels of plasma t-PA: Ag (9.45 ng/ml ± 1.18 in nephrotic patients versus 5.8 ng/ml ± 1.23 in controls before venous occlusion and respectively 33.1 ng/ml ± 3.83 versus 20.3 ± 3.40 in controls after venous occlusion). Plasminogen activator activity of the euglobulins as assessed by the bovine fibrin-agarose plate was significantly higher in nephrotic patients only after venous occlusion. Plasma samples of nephrotic patients exerted a more potent inhibition of fibrinolysis in a urokinase activated system. This effect was, however, mainly due to the high levels of α2 macroglobulin in nephrotic plasma which apparently have little influence on dilute blood clot lysis time.

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Clinical studies on plasma fibronectin and factor XIII; with special reference to hyperlipoproteinemia

Cited by 12 publications

References 20 publications

Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cells

Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cells

Correlation between Plasma Fibrinogen and Serum Lipids in Rats with Hyperlipidemia Induced by Cholesterol Free-High Fructose or High Cholesterol Diet.

Tissue-Type Plasminogen Activator (t-PA) and Dilute Blood Clot Lysis Time in Nephrotic Patients

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