Circulating Neuregulin-1 and Chronic Heart Failure with Preserved Ejection

Abstract

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.

Deciphering the Active Compounds and Mechanisms of HSBDF for Treating ALI via Integrating Chemical Bioinformatics Analysis

“…Also, studies have shown that the HIF-1α signaling pathway was related to inflammation, and arginine can regulate HIF-1α to suppress the inflammatory response ( Chen et al, 2020 ). The Er7bB signaling pathway was associated with oxidative stress, and it was reported that the ErbB4 system of the heart was activated at early stages of chronic heart failure to enhance the cardiomyocyte resistance to oxidative stress ( Shchendrigina et al, 2020 ). The TNF signaling pathways and inflammatory pathways can suppress inflammation ( Liang et al, 2021 ).…”

Serum levels of neuregulin-1 in patients with coronary artery disease: clinical and pathogenetic aspects

“…Необходимо отметить ряд работ по изучению уровня NRG-1 у пациентов с ХСН в зависимости от ее генеза, а также тяжести клинических проявлений [13][14][15][16][17][18]. В исследовании Ky B, et al [13] обнаружено значимое повышение уровня NRG-1β у пациентов с IV ФК СН согласно классификации NYHA в сравнении с I ФК и выявлена независимая связь с повышенным риском смертельных исходов или трансплантации сердца.…”