The Effect of Reagents Mimicking Oxidative Stress on Fibrinogen Function

Abstract

Fibrinogen is one of the plasma proteins most susceptible to oxidative modification. It has been suggested that modification of fibrinogen may cause thrombotic/bleeding complications associated with many pathophysiological states of organism. We exposed fibrinogen molecules to three different modification reagents—malondialdehyde, sodium hypochlorite, and peroxynitrite—that are presented to various degrees in different stages of oxidative stress. We studied the changes in fibrin network formation and platelet interactions with modified fibrinogens under flow conditions. The fastest modification of fibrinogen was caused by hypochlorite. Fibers from fibrinogen modified with either reagent were thinner in comparison with control fibers. We found that platelet dynamic adhesion was significantly lower on fibrinogen modified with malondialdehyde and significantly higher on fibrinogen modified either with hypochlorite or peroxynitrite reflecting different prothrombotic/antithrombotic properties of oxidatively modified fibrinogens. It seems that, in the complex reactions ongoing in living organisms at conditions of oxidation stress, hypochlorite modifies proteins (e.g., fibrinogen) faster and more preferentially than malondialdehyde. It suggests that the prothrombotic effects of prior fibrinogen modifications may outweigh the antithrombotic effect of malondialdehyde-modified fibrinogen in real living systems.

In vitro study on the deterioration of polypropylene hernia repair meshes

“…It is believed that this in vitro system provides a sufficient correlation with the in vivo oxidative stress. 20,36 The hypochlorite concentration used in this study is somewhat similar to the local concentration observed in natural systems at the inflammatory site. 37,38 It is important to emphasize that both approaches used herein to mimic the in vivo oxidative environment at the tissue-biomaterial interface have never been applied to study hernia repair meshes.…”

“…In an attempt to simulate the effect of hypochlorite anions produced by MPO, the meshes were treated in a sodium hypochlorite solution with a concentration of 1 m M . It is believed that this in vitro system provides a sufficient correlation with the in vivo oxidative stress . The hypochlorite concentration used in this study is somewhat similar to the local concentration observed in natural systems at the inflammatory site .…”

“…The effect of hypochlorite on the prosthetic mesh materials was tested according to the protocol described elsewhere. 20 Briefly, the meshes were treated in 100 mL of 1 mM NaOCl solution (Sigma-Aldrich, St Louis, MO) for 40 days at 378C. After the treatment, the meshes were rinsed with 500 mL of distilled water and air-dried at room temperature.…”

The clinical relevance of altered fibrinogen packaging in the presence of 17β-estradiol and progesterone

“…Plasma fibrinogen is susceptible to oxidative stress [35], and fibrinogen exposed to reagents present during oxidative stress resulted in decreased fibrin fiber diameter [36].…”

In Vitro Susceptibility of Wistar Rat Platelets to Hydrogen Peroxide and AAPH-Induced Oxidative Stress

“…Anorexia nervosa, associated with high cardiovascular mortality is related to reduced L-arginine transport, NOS activity and cGMP basal levels in platelets due to increased OS [10]. Fibrinogen (Factor X) is one of the plasma proteins most susceptible to oxidative modification, which may cause thrombotic/ bleeding complications associated with many pathophysiological states [11]. Hence, platelet OS and intra-platelet redox control are basic research subjects of relevance for understanding the involvement of platelets in atherogenic, inflammatory and antigenic processes, beyond their crucial role in haemostasis and thrombosis.…”