Effects of Dietary Fat Quality and Quantity on Postprandial Activation of Blood Coagulation Factor VII

Abstract Context: Type 2 diabetes mellitus (T2DM) is a hypercoagulable state. Tissue factor (TF) is the principal initiator of blood coagulation. Objective: Our objective was to examine the effects of hyperglycemia and hyperinsulinemia on the TF pathway of blood coagulation in T2DM. Design: Three study protocols were used: 1) acute correction of hyperglycemia (with iv insulin) followed by 24 h of euglycemia, 2) 24 h of selective hyperinsulinemia, and 3) 24 h of combined hyperinsulinemia and hyperglycemia. Setting: The study took place at a clinical research center. Study Participants: Participants included 18 T2DM patients and 22 nondiabetic controls. Results: Basal TF-procoagulant activity (TF-PCA), monocyte TF mRNA, plasma coagulation factor VII (FVIIc), and thrombin-anti-thrombin complexes were higher in T2DM than in nondiabetic controls, indicating a chronic procoagulant state. Acutely normalizing hyperglycemia over 2–4 h resulted in a small (∼7%) but significant decline in TF-PCA with no further decline over 24 h. Raising insulin levels alone raised TF-PCA by 30%, whereas raising insulin and glucose levels together increased TF-PCA (by 80%), thrombin-anti-thrombin complexes, and prothrombin fragment 1.2. Plasma FVIIa and FVIIc declined with increases in TF-PCA. Conclusion: We conclude that the combination of hyperglycemia and hyperinsulinemia, common in poorly controlled patients with T2DM, contributes to a procoagulant state that may predispose these patients to acute cardiovascular events.

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Effects of dietary fat quantity and composition on fasting and postprandial levels of coagulation factor VII and serum choline-containing phospholipids

British Journal Of Nutrition ◽

10.1079/bjn2003911 ◽

2003 ◽

Vol 90 (2) ◽

pp. 329-336 ◽

Cited By ~ 3

Author(s):

Anja Schou Lindman ◽

Hanne Müller ◽

Ingebjørg Seljeflot ◽

Hans Prydz ◽

Marit Veierød ◽

...

Keyword(s):

Fatty Acids ◽

Dietary Fat ◽

High Fat Diet ◽

Unsaturated Fatty Acids ◽

Saturated Fatty Acids ◽

Coagulation Factor ◽

Factor Vii ◽

High Fat ◽

Coagulation Factor Vii ◽

Low Fat Diet

Dietary fat influences plasma levels of coagulation factor VII (FVII) and serum phospholipids (PL). It is, however, unknown if the fat-mediated changes in FVII are linked to PL. The present study aimed to investigate the effects of dietary fat on fasting and postprandial levels of activated FVII (FVIIa), FVII coagulant activity (FVIIc), FVII protein (FVIIag) and choline-containing PL (PC). In a randomized single-blinded crossover-designed study a high-fat diet (HSAFA), a low-fat diet (LSAFA), both rich in saturated fatty acids, and a high-fat diet rich in unsaturated fatty acids (HUFA) were consumed for 3 weeks. Twenty-five healthy females, in which postprandial responses were studied in a subset of twelve, were included. The HSAFA diet resulted in higher levels of fasting FVIIa and PC compared with the LSAFA and the HUFA diets (all comparisonsP≤0·01). The fasting PC levels after the LSAFA diet were also higher than after the HUFA diet (P<0·001). Postprandial levels of FVIIa and PC were highest on the HSAFA diet and different from LSAFA and HUFA (all comparisonsP≤0·05). Postprandial FVIIa was higher on the HUFA compared with the LSAFA diet (P<0·03), whereas the HUFA diet resulted in lower postprandial levels of PC than the LSAFA diet (P<0·001). Significant correlations between fasting levels of PC and FVIIc were found on all diets, whereas FVIIag was correlated to PC on the HSAFA and HUFA diet. The present results indicate that dietary fat, both quality and quantity, influences fasting and postprandial levels of FVIIa and PC. Although significant associations between fasting FVII and PC levels were found, our results do not support the assumption that postprandial FVII activation is linked to serum PC.

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The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein

Scandinavian Journal of Clinical and Laboratory Investigation ◽

10.1080/00365510050185038 ◽

2000 ◽

Vol 60 (1) ◽

pp. 45-54 ◽

Cited By ~ 16

Author(s):

L. F. Larsen, P. Marckmann, E.-M. B

Keyword(s):

Blood Coagulation ◽

Coagulation Factor ◽

Factor Vii ◽

High Fat ◽

Coagulation Factor Vii

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Characterization of Transcriptional Regulatory Elements in the Promoter Region of the Murine Blood Coagulation Factor VII Gene

Journal of Biological Chemistry ◽

10.1074/jbc.273.4.2277 ◽

1998 ◽

Vol 273 (4) ◽

pp. 2277-2287 ◽

Cited By ~ 16

Author(s):

Daniel R. Stauffer ◽

Beatrice N. Chukwumezie ◽

Julie A. Wilberding ◽

Elliot D. Rosen ◽

Francis J. Castellino

Keyword(s):

Blood Coagulation ◽

Promoter Region ◽

Coagulation Factor ◽

Regulatory Elements ◽

Factor Vii ◽

Transcriptional Regulatory Elements ◽

Coagulation Factor Vii ◽

Transcriptional Regulatory

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Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor

Human Reproduction ◽

10.1093/humrep/17.12.3235 ◽

2002 ◽

Vol 17 (12) ◽

pp. 3235-3241 ◽

Cited By ~ 31

Author(s):

E.M. Bladbjerg

Keyword(s):

Hormone Replacement Therapy ◽

Replacement Therapy ◽

Tissue Factor ◽

Blood Coagulation ◽

Tissue Factor Pathway Inhibitor ◽

Hormone Replacement ◽

Coagulation Factor ◽

Factor Vii ◽

Coagulation Factor Vii ◽

Tissue Factor Pathway

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The Effect of O-Fucosylation on the First EGF-like Domain from Human Blood Coagulation Factor VII†

Biochemistry ◽

10.1021/bi990234z ◽

1999 ◽

Vol 38 (22) ◽

pp. 7097-7110 ◽

Cited By ~ 34

Author(s):

Yung-Hsiang Kao ◽

Geoffrey F. Lee ◽

Yang Wang ◽

Melissa A. Starovasnik ◽

Robert F. Kelley ◽

...

Keyword(s):

Blood Coagulation ◽

Human Blood ◽

Coagulation Factor ◽

Factor Vii ◽

Coagulation Factor Vii ◽

Human Blood Coagulation

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A candidate activation pathway for coagulation factor VII

Biochemical Journal ◽

10.1042/bcj20190595 ◽

2019 ◽

Vol 476 (19) ◽

pp. 2909-2926

Author(s):

Tina M. Misenheimer ◽

Kraig T. Kumfer ◽

Barbara E. Bates ◽

Emily R. Nettesheim ◽

Bradford S. Schwartz

Keyword(s):

Tissue Factor ◽

Blood Coagulation ◽

Factor Viia ◽

Coagulation Factor ◽

Factor Ix ◽

Factor Vii ◽

Factor X ◽

Contact Activation ◽

Coagulation Factor Vii ◽

Factor Viiia

Abstract The mechanism of generation of factor VIIa, considered the initiating protease in the tissue factor-initiated extrinsic limb of blood coagulation, is obscure. Decreased levels of plasma VIIa in individuals with congenital factor IX deficiency suggest that generation of VIIa is dependent on an activation product of factor IX. Factor VIIa activates IX to IXa by a two-step removal of the activation peptide with cleavages occurring after R191 and R226. Factor IXaα, however, is IX cleaved only after R226, and not after R191. We tested the hypothesis that IXaα activates VII with mutant IX that could be cleaved only at R226 and thus generate only IXaα upon activation. Factor IXaα demonstrated 1.6% the coagulant activity of IXa in a contact activation-based assay of the intrinsic activation limb and was less efficient than IXa at activating factor X in the presence of factor VIIIa. However, IXaα and IXa had indistinguishable amidolytic activity, and, strikingly, both catalyzed the cleavage required to convert VII to VIIa with indistinguishable kinetic parameters that were augmented by phospholipids, but not by factor VIIIa or tissue factor. We propose that IXa and IXaα participate in a pathway of reciprocal activation of VII and IX that does not require a protein cofactor. Since both VIIa and activated IX are equally plausible as the initiating protease for the extrinsic limb of blood coagulation, it might be appropriate to illustrate this key step of hemostasis as currently being unknown.

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