[Oxidized fibrinogen and its relationship with hemostasis disturbances and endothelial dysfunction during coronary heart disease and myocardial infarction].

The highest oxidative modification of fibrinogen was found in acute myocardial infarction (MI) men and it was 1.26 and 1.56 times higher in comparison with coronary heart disease (CHD) men with anamnesis of MI and with men without CHD, respectively. Increased oxidized fibrinogen level correlated with increased levels of plasma lipid peroxidation products, Willebrand factor, fibrin degradation products, accelerated leukocyte-platelet aggregation and decreased level of plasma NO metabolites. Associations of oxidized fibrinogen with MI and typical parameters of thrombosis and hypercoagulatory hemostasis disturbances and endothelial function were revealed.

[Procedure for determination of oxidative modification of plasma fibrinogen].

The purpose of the present study was to develop a new procedure for determining the oxidative modification of plasma fibrinogen. The procedure was developed to use blood plasma from 96 males aged 35-60 years who had cardiovascular diseases: 49 patients with coronary heart disease (CHD), including 16 patients with sub-acute myocardial infarction (MI), and 47 patients with arterial hypertension without CHD. The new procedure is as follows: a rapid fibrin isolating method, a reaction with 2,4-dinitrophenylhydrazine in 2 M HCl solution, by subsequently rinsing in the ethanol : ethyl acetate (1:1) solution, dissolving the precipitate in 8 M urea, and by determining the level of the resultant dinitrophenylhydrazones by spectrophotometry at 363 nm, followed by conversion to the plasma concentration of fibrinogen. The procedure is of informative value for the degree of oxidative fibrinogen modification under oxidative stress; it is technically simple, takes little time, and shows a good reproducibility. The values of determined oxidized plasma fibrinogen by the developed procedure show a high positive correlation with the estimates of oxidized total blood protein fraction and with the values of blood lipid peroxidation. The detected elevated level of oxidized fibrinogen in CHD and MI suggests that this index is a new diagnostic marker of oxidative stress in cardiovascular diseases of atherosclerotic genesis.

[Deletional polymorphism of the 11th intron of the human c-fms gene: allele frequency in certain Russian populations and possible functional significance]. / Deletsionnyi polimorfizm 11-go introna gena c-fms cheloveka: chastoty allelei v nekotorykh populiatsiiakh Rossii i vozmozhnaia funktsional'naia znachimost'.

Analysis of deletion polymorphism of human c-fms gene intron 11 (approximately 425-bp deletion) is of particular interest because of the increased proportion of the deletion heterozygotes among the infants born from the parents, one of which lacks the deletion allele, and the other is heterozygous for the deletion. In this study, allele and haplotype frequencies of the polymorphism examined were assessed in a number of Caucasoid and Mongoloid populations of Russia. In all populations tested, relatively high prevalence of the deletion-bearing allele, ranging from 9.45% in ethnic Germans to 20.75% in Altaians, was detected. Russians and Kazakhs were characterized by intermediate frequencies of the rare allele, constituting in these populations 12.89 and 14.93%, respectively. Hardy-Weinberg expectations were met in all populations examined, pointing to a stable level of polymorphism at the c-fms intron 11. It was established by the context analysis of DNA of the deleted fragment along with the flanking sequences that this region contained a number of transcription factor motifs (Ets, SRF, and Myc), potentially capable of the regulation of the M-CFF-dependant c-fms transcription. The deletion breakpoint was localized within the CArG motif, which, together with the neighboring ets motif, form the potential CArG/ets composite element. It was suggested that allele lacking the fragment of intron 11 could be restricted in its ability to modulate the level of the c-fms transcription in response to the action of M-CSF. The data of molecular epidemiological survey serve as the indirect evidence favoring the suggestion on the possible functional value of this gene fragment. It was demonstrated that in the samples of acute bronchitis and trichomoniasis patients allelic and genotype frequencies were statistically significantly different from those in the population sample. In case of trichmoniasis, the frequency of rare allele was 2.4 times lower, and in case of acute bronchitis it was 2.1 times higher than in the control sample.

Relationship between oxidized fibrinogen and hemostasis disturbances and endothelial dysfunction in myocardial infarction.

Oxidative modification of fibrinogen in acute myocardial infarction increased 1.3-fold compared to that in CHD and 1.5-fold surpassed that in the control without CHD. Elevated content of oxidized fibrinogen correlated with increased levels of LPO products, von Willebrand factor, and fibrin degradation products, with accelerated leukocyte and platelet aggregation, and reduced content of NO metabolites in the plasma. Independent associations of oxidized fibrinogen with myocardial infarction and typical thrombogenic and hypercoagulation hemostasis disorders and endothelial dysfunctions were revealed.