Fructose induces prothrombotic phenotype in human endothelial cells : A new role for "added sugar" in cardio-metabolic risk.

Abstract

Intake of large amounts of added sweeteners has been associated with the pathogenesis of cardiometabolic risk. Several studies have shown that fructose increases the cardiovascular risk by modulating endothelial dysfunction and promoting atherosclerosis. Recently, a potential role for fructose in cardiovascular thrombosis has been suggested but with controversial results. Tissue factor (TF) plays a pivotal role in the pathophysiology of cardiovascular thrombosis by triggering the formation of intracoronary thrombi following endothelial injury. This study investigates the effects of fructose, in a concentration range usually observed in the plasma of patients with increased cardiovascular risk, on TF in human umbilical endothelial cells (HUVECs). Cells were stimulated with increasing concentrations of fructose (0.25, 1 and 2.5 mM) and then processed to evaluate TF-mRNA levels by real-time PCR as well as TF expression/activity by FACS analysis and procoagulant activity. Finally, a potential molecular pathway involved in modulating this phenomenon was investigated. We demonstrate that fructose induces transcription of mRNA for TF. In addition, we show that this monosaccharide promotes surface expression of TF that is functionally active. Fructose effects on TF appear modulated by the oxygen free radicals through activation of the transcription factor NF-κB since superoxide dismutase and NF-κB inhibitors suppressed TF expression. Data of the present study, although in vitro, indicate that fructose, besides promoting atherosclerosis, induces a prothrombotic phenotype in HUVECs, thus indicating one the mechanism(s) by which this sweetener might increase cardiometabolic risk.

• Authors: Plinio Cirillo, Grazia Pellegrino, Stefano Conte, Fabio Maresca, Francesco Pacifico, Antonio Leonardi, Bruno Trimarco
• Journal: Journal of thrombosis and thrombolysis (J Thromb Thrombolysis) Vol. 40 Issue 4 Pg. 444-51 (Nov 2015) ISSN: 1573-742X [Electronic] Netherlands
• PMID: 26104185 (Publication Type: Journal Article)

Chemical References

• NF-kappa B
• Sweetening Agents
• Fructose
• Thromboplastin

Topics

• Atherosclerosis (chemically induced, metabolism, pathology)
• Fructose (adverse effects, pharmacokinetics, pharmacology)
• Gene Expression Regulation (drug effects)
• Human Umbilical Vein Endothelial Cells (metabolism, pathology)
• Humans
• NF-kappa B (metabolism)
• Sweetening Agents (adverse effects, pharmacology)
• Thromboplastin (biosynthesis)
• Thrombosis (chemically induced, metabolism, pathology)
• Transcription, Genetic (drug effects)