Vitamin C suppresses lipopolysaccharide-induced procoagulant response of human monocyte-derived macrophages

M.S. Parahuleva, J. Jung, M. Burgazli, A. Erdogan, B. Parviz, H. Hölschermann

Internal Medicine/Cardiology and Angiology, University Hospital of Giessen and Marburg, Giessen, Germany. mariana.parahuleva@innere.med.uni-giessen.de

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• Pharmacology

OBJECTIVE: Although vitamin C is a strong antioxidant, the epidemiologic evidence to support its role in lowering risk of cardiovascular disease is inconsistent. In order to define the role of vitamin C in vascular pathophysiology, we have investigated the effect of vitamin C on the tissue factor (TF) and Factor VII Activating Protease (FSAP) expression induced by lipopolysaccharide (LPS) in human monocyte-derived macrophages.

MATERIALS AND METHODS: Vitamin C at clinically relevant doses was tested to its ability to influence the LPS- and reactive oxygen species (ROS) – generating system of xanthine/xanthine oxidase (X/XO) NF-kB activity in human monocyte-derived macrophages.

RESULTS: Vitamin C-treatment prevents LPS- and ROS-induced DNA-binding activity of NF-kB in a concentration-dependent fashion. Vitamin C also inhibited the phosphorylation and proteolytic degradation of the inhibitor protein IkBa. In parallel to regulate NF-kB activity, vitamin C reduced the expression of TF and FSAP, genes known to be induced by bacterial LPS and triggered the extrinsic coagulation cascade and linked thrombosis with inflammation.

CONCLUSIONS: Vitamin C alters pro-inflammatory and pro-coagulatory processes via inhibition of NF-kB activation and exerts beneficial antiatherogenic effects on human monocyte-derived macrophages in addition to its anti-oxidant properties.

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