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. 2012 Aug 4;3(8):627–640. doi: 10.1007/s13238-012-2057-y

Reactive carbonyl compounds (RCCs) cause aggregation and dysfunction of fibrinogen

Ya-Jie Xu 1, Min Qiang 1,2, Jin-Ling Zhang 1, Ying Liu 1, Rong-Qiao He 1,3,✉
PMCID: PMC4875355  PMID: 22836718

Abstract

Fibrinogen is a key protein involved in coagulation and its deposition on blood vessel walls plays an important role in the pathology of atherosclerosis. Although the causes of fibrinogen (fibrin) deposition have been studied in depth, little is known about the relationship between fibrinogen deposition and reactive carbonyl compounds (RCCs), compounds which are produced and released into the blood and react with plasma protein especially under conditions of oxidative stress and inflammation. Here, we investigated the effect of glycolaldehyde on the activity and deposition of fibrinogen compared with the common RCCs acrolein, methylglyoxal, glyoxal and malondialdehyde. At the same concentration (1 mmol/L), glycolaldehyde and acrolein had a stronger suppressive effect on fibrinogen activation than the other three RCCs. Fibrinogen aggregated when it was respectively incubated with glycolaldehyde and the other RCCs, as demonstrated by SDS-PAGE, electron microscopy and intrinsic fluorescence intensity measurements. Staining with Congo Red showed that glycolaldehyde- and acrolein-fibrinogen distinctly formed amyloid-like aggregations. Furthermore, the five RCCs, particularly glycolaldehyde and acrolein, delayed human plasma coagulation. Only glycolaldehyde showed a markedly suppressive effect on fibrinogenesis, none did the other four RCCs when their physiological blood concentrations were employyed, respectively. Taken together, it is glycolaldehyde that suppresses fibrinogenesis and induces protein aggregation most effectively, suggesting a putative pathological process for fibrinogen (fibrin) deposition in the blood.

Electronic Supplementary Material

The online version of this article (doi:10.1007/s13238-012-2057-y contains supplementary material, which is available to authorized users.

Keywords: fibrinogen, acrolein, glycolaldehyde, glyoxal, malondialdehyde, methylglyoxal

Electronic Supplementary Material

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Footnotes

These authors contributed equally to the work.

Electronic Supplementary Material

The online version of this article (doi:10.1007/s13238-012-2057-y contains supplementary material, which is available to authorized users.

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