Chronic heart failure (CHF) with preserved ejection fraction (CHFpEF) is an unsolved, socially relevant challenge since it is associated with a high level of morbidity and mortality. Early markers for this pathology are unavailable, and therapeutic approaches are undeveloped. This necessitates extensive studying the mechanisms of CHFpEF to identify therapeutic targets. According to current notions, systemic inflammation and endothelial dysfunction play an important role in the pathogenesis of CHFpEF. These processes induce the development of myocardial fibrosis and impairment of cardiomyocyte relaxation, thereby resulting in diastolic dysfunction and increased left ventricular (LV) filling pressure. Neuregulin-1 (NRG-1) is a paracrine growth factor and a natural agonist of ErbB receptor family synthesized in the endothelium of coronary microvessels. The NRG-1 / ErbB4 system of the heart is activated at early stages of CHFpEF to enhance the cardiomyocyte resistance to oxidative stress. Preclinical and clinical (phases II and III) studies have shown that the recombinant NRG-1 therapy results in improvement of myocardial contractility and in LV reverse remodeling. Results of recent studies suggest possible anti-inflammatory and antifibrotic effects of NRG-1, which warrants studying the activity of this system in patients with CHFpEF.
A new approach for the evaluation of oxidizability of proteins and lipids in the same sample of blood plasma was proposed. We tested a method for evaluation of metal-catalyzed oxidation of fibrinogen by the formation of bityrosine cross-links during oxidation detected by the increase in fluorescence at 415 nm. A correlation was revealed between parameters of oxidizability estimated by this marker and carbonyl derivatives (dinitrophenylhydrazine method). Oxidizability of total proteins from whole plasma was compared with oxidizability of plasma lipids (marker malonic dialdehyde). Study of these parameters in patients with coronary heart disease showed that the proposed experimental approach allows us to divide the sample into several subgroups differing in the resistance to oxidative stress. These data can be used for diagnostic and prognostic purposes.
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