Long-Chain n-3 Fatty Acids Specifically Affect Rat Coagulation Factors Dependent on Vitamin K

Leray, Claude; Wiesel, Marie-Louise; Freund, Monique; Cazenave, Jean‐Pierre; Gachet, Christian

doi:10.1161/01.atv.21.3.459

Cited by 28 publications

(16 citation statements)

References 48 publications

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“…Our finding that infusion of DHA in mice increased hepatic lipid peroxide content is consistent with a large body of literature, primarily from studies of animals fed on diets enriched in PUFAs (45,(64)(65)(66)(67). For example, feeding rats on diets enriched in EPA, DHA, or LNA increased hepatic lipid peroxidation and the breakdown of vitamin E (64).…”

Section: Figuresupporting

confidence: 87%

Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production

Pan¹,

Cederbaum²,

Zhang³

et al. 2004

J. Clin. Invest.

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How ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) lower plasma lipid levels is incompletely understood. We previously showed that marine ω-3 PUFAs (docosahexaenoic acid [DHA] and eicosapentaenoic acid) stimulate a novel pathway, post-ER presecretory proteolysis (PERPP), that degrades apolipoprotein B100 (ApoB100), thereby reducing lipoprotein secretion from liver cells. To identify signals stimulating PERPP, we examined known actions of ω-3 PUFA. In rat hepatoma or primary rodent hepatocytes incubated with ω-3 PUFA, cotreatment with the iron chelator desferrioxamine, an inhibitor of iron-dependent lipid peroxidation, or vitamin E, a lipid antioxidant, suppressed increases in thiobarbituric acid-reactive substances (TBARSs; a measure of lipid peroxidation products) and restored ApoB100 recovery and VLDL secretion. Moreover, ω-6 and nonmarine ω-3 PUFA, also prone to peroxidation, increased ApoB100 degradation via intracellular induction of TBARSs. Even without added fatty acids, degradation of ApoB100 in primary hepatocytes was blocked by desferrioxamine or antioxidant cotreatment. To extend these results in vivo, mice were infused with DHA, which increased hepatic TBARSs and reduced VLDL-ApoB100 secretion. These results establish a novel link between lipid peroxidation and oxidant stress with ApoB100 degradation via PERPP, and may be relevant to the hypolipidemic actions of dietary PUFAs, the basal regulation of ApoB100 secretion, and hyperlipidemias arising from ApoB100 overproduction.

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Section: Figuresupporting

confidence: 87%

Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production

Pan¹,

Cederbaum²,

Zhang³

et al. 2004

J. Clin. Invest.

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“…Such association between PUFA and ETP is consistent with our findings in rats. The physiological relevance of omega-3 PUFA in ETP regulation may be explained by interference with 41,42 or by other phenomena. 43,44 Although diet composition was enriched in vitamin K-containing nutrients, the lack of change in protein C and free protein S after healthy diet strongly suggests that vitamin K was not involved in diet-induced ETP regulation.…”

mentioning

confidence: 99%

Diet Modulates Endogenous Thrombin Generation, A Biological Estimate of Thrombosis Risk, Independently of the Metabolic Status

Sánchez

Poggi

Morange

et al. 2012

ATVB

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Objective— High endogenous thrombin potential (ETP) is associated with venous and arterial thrombosis. Better knowledge of environmental influences on ETP may help to prevent thrombosis. Methods and Results— Weaning rats exhibited high ETP values that decreased in low-fat diet and remained elevated on high-fat diet. In adult rats, high-fat diet–induced ETP increase was independent of coagulation factors, obesity, and insulin resistance and negatively associated with polyunsaturated fatty acid levels. Switching from high-fat diet to low-fat diet reversed the procoagulant phenotype with a slower kinetic than the normalization of hyperinsulinemia. In humans, ETP was independent of body weight whereas it was negatively associated with nutritional markers such as the percentage of energy provided by proteins, the protein:fat ratio, circulating phenolic compounds, and omega-3 polyunsaturated fatty acid. A recommended 3-month healthy diet with reduced energy density, including lipids, decreased ETP (−21%; P <0.0001). Changes in ETP were not associated with body weight, insulin sensitivity, or coagulation factor variations, but correlated negatively with plasma docosahexaenoic acid, a nutritional status sensitive fatty acid, and compounds reflecting vegetable intake. Conclusion— Diet plays a pivotal role in regulating ETP, independently of obesity and insulin resistance. Global nutritional recommendations could be useful in primary prevention of venous thrombosis.

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“…[60,61] In contrast, views on the mechanisms underlying the anticoagulant effects of n-3 PUFAs remain controversial. Some studies suggest these molecules may interfere in the carboxylation of vitamin K-dependent coagulation factors II, VII, IX and X; [62,63] while other studies attribute more relevance to a modification in serum fibrinogen levels.…”

Section: Thrombogenesismentioning

confidence: 99%

Omega-3 polyunsaturated fatty acids and cardiovascular health: a molecular view into structure and function

Calvo¹,

Martínez²,

Torres³

et al. 2017

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How to cite this article: Calvo MJ, Martínez MS, Torres W, Chávez-Castillo M, Luzardo E, Villasmil N, Salazar J, Velasco M, Bermúdez V. Omega-3 polyunsaturated fatty acids and cardiovascular health: a molecular view into structure and function. Vessel Plus 2017;1:116-28.Given the notorious impact of cardiovascular disease (CVD) as the current leading cause of mortality worldwide, the prevention, identification and management of CV risk factors represents a priority in daily clinical practice. Several studies have shown the beneficial effects of dietary omega-3 polyunsaturated fatty acids (PUFAs) on CV health. Their derivatives, eicosapentaenoic acid and docosahexaenoic acid, intervene in multiple metabolic pathways, including: regulation of the inflammatory response, by reducing the synthesis of pro-inflammatory cytokines; regulation of platelet aggregation, activation and adhesion, by modulating thromboxane A2 and plasminogen activator inhibitor-1 activity; regulation of the coagulation pathways, by reducing the carboxylation of vitamin K-dependent coagulation factors; improvement of endothelial function, given their effects on prostaglandin synthesis and endothelial nitric oxide synthase; reduction of serum lipids, through their effects on the hepatic synthesis of triacylglycerides, beta-oxidation of fatty acids and lipoprotein catabolism; and improvement of myocardial function via their membrane-stabilizing effects, and an increase in fluidity, size and distribution of membrane lipid rafts. Nevertheless, these effects appear to vary according to the type of PUFA ingested, dietary sources, daily dosing and individual factors inherent to the subject. Therefore, further studies are required to determine the ideal supplementation for each kind of patient and their particular CV profiles. Key words:Cardiovascular disease, omega-3 polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaeonic acid ABSTRACTArticle history:

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Long-Chain n-3 Fatty Acids Specifically Affect Rat Coagulation Factors Dependent on Vitamin K

Cited by 28 publications

References 48 publications

Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production

Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production

Diet Modulates Endogenous Thrombin Generation, A Biological Estimate of Thrombosis Risk, Independently of the Metabolic Status

Omega-3 polyunsaturated fatty acids and cardiovascular health: a molecular view into structure and function

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