Soluble ST2 protein in chronic heart failure is independent of traditional factors

Introduction

ST2 protein is the interleukin 33 (IL-33) receptor, whose serum level depends on the biomechanical strain of cardiac myocytes. The aim of this study was to analyse the relationship between soluble ST2 (sST2) level and traditional factors in patients with chronic heart failure.

Material and methods

Sixty-six patients (mean age 62 years, 75% males) in stable NYHA class I-III with left ventricular ejection fraction < 45% were included in the study. Clinical, biochemical, electrocardiographic, echocardiographic and angiographic data were analysed. Patients were divided into groups depending on sST2 median: > 0.28 ng/ml (n = 31) vs. ≤ 0.28 ng/ml (n = 35). sST2 was measured using a quantitative ELISA kit. In order to define factors associated with sST2 levels uni- and multivariate regression analysis was performed.

Results

There was no relationship between sST2 levels and age (p = 0.67), body mass index (p = 0.19), hsTnT (p = 0.7) or other analysed parameters (all p > 0.05), except for N-terminal prohormone B-type natriuretic peptide (NT-proBNP). A significant positive correlation between sST2 and NT-proBNP was found (p = 0.013, R = 0.395). Multivariate analysis revealed that the stage of coronary artery disease and NT-proBNP were independent factors associated with sST2 concentration (p = 0.04). Intriguing is the fact that the fewer the sclerotic changes present in arteries, the higher was the sST2 level (β = –0.381, p = 0.04).

Conclusions

sST2 protein is independent of traditional factors which usually affect levels of NT-proBNP. In chronic heart failure, sST2 protein may be of greater importance in idiopathic dilated cardiomyopathy than in ischaemic aetiology, which seems to be associated with the molecular mechanism (biomechanical strain) related to sST2.     

Mechanisms underlying the developmental origins of disease

It is well established that there is a relationship between patterns of early growth and subsequent risk of development of metabolic diseases such as type 2 diabetes and cardiovascular disease. Studies in both humans and in animal models have provided strong evidence that the early environment plays an important role in mediating these relationships. The concept of the developmental origins of health and disease is therefore widely accepted. The mechanisms by which an event in very early life can have a permanent effect on the long-term health of an individual are still relatively poorly understood. However a growing body of evidence has implicated a number of candidate mechanisms. These include permanent changes in an organ structure, programmed changes in gene expression through epigenetic modifications and persistent effects on regulation of cellular ageing. Understanding the extent and nature of these processes may enable the identification of individuals at risk of metabolic disease as well as providing insight into potential preventative and intervention strategies.     

Inhibitory effect of N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide on Haemophilus spp. planktonic or biofilm-forming cells

During this study, we have investigated in vitro activity of N-substituted-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide derivatives with N-ethyl, N-(4-metoxyphenyl) and N-cyclohexyl substituents against Gram-negative Haemophilus influenzae and H. parainfluenzae bacteria. A spectrophotometric assay was used in order to determine the bacterial growth and biofilm formation using a microtiter plate to estimate minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MBIC). Among the tested N-substituted pyrazole derivatives, only N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide showed a significant in vitro activity against both planktonic cells of H. parainfluenzae (MIC = 0.49–31.25 μg ml^?1) and H. influenzae (MIC = 0.24–31.25 μg ml^?1) as well as biofilm-forming cells of H. parainfluenzae (MBIC = 0.24–31.25 μg ml^?1) and H. influenzae (MBIC = 0.49 to ≥31.25 μg ml^?1). The pyrazole compound exerted higher inhibitory effect both on the growth of planktonic cells and biofilm formation by penicillinase-positive and penicillinase-negative isolates of H. parainfluenzae than the activity of commonly used antibiotics such as ampicillin. No cytotoxicity of the tested compound in vitro at concentrations used was found. The tested pyrazole N-ethyl derivative could be considered as a compound for the design of agents active against both pathogenic H. influenzae and opportunistic H. parainfluenzae, showing also anti-biofilm activity. This appears important because biofilms are determinants of bacterial persistence in long-term and recurrent infections recalcitrant to standard therapy.