Adrenomedullin and endothelin-1 are related to inflammation in chronic heart failure.

Vasoregulation and inflammation may be connected in heart failure patients independently of the disease severity. The observed link may contribute to the understanding of the complex pathomechanism in CHF

ATP-dependent conformational dynamics in a photoactivated adenylate cyclase revealed by fluorescence spectroscopy and small-angle X-ray scattering

International audienceAbstract Structural insights into the photoactivated adenylate cyclases can be used to develop new ways of controlling cellular cyclic adenosine monophosphate (cAMP) levels for optogenetic and other applications. In this work, we use an integrative approach that combines biophysical and structural biology methods to provide insight on the interaction of adenosine triphosphate (ATP) with the dark-adapted state of the photoactivated adenylate cyclase from the cyanobacterium Oscillatoria acuminata (OaPAC). A moderate affinity of the nucleotide for the enzyme was calculated and the thermodynamic parameters of the interaction have been obtained. Stopped-flow fluorescence spectroscopy and small-angle solution scattering have revealed significant conformational changes in the enzyme, presumably in the adenylate cyclase (AC) domain during the allosteric mechanism of ATP binding to OaPAC with small and large-scale movements observed to the best of our knowledge for the first time in the enzyme in solution upon ATP binding. These results are in line with previously reported drastic conformational changes taking place in several class III AC domains upon nucleotide binding

Elevated extracellular HSP70 (HSPA1A) level as an independent prognostic marker of mortality in patients with heart failure

Predicting the survival of a patient with heart failure (HF) is a complex problem in clinical practice. Our previous study reported that extracellular HSP70 (HSPA1A) correlates with markers of heart function and disease severity in HF, but the predictive value of HSP70 is unclear. The goal of this study was to analyze extracellular HSP70 as predictive marker of mortality in HF. One hundred ninety-five patients with systolic heart failure were enrolled and followed up for 60 months. By the end of follow-up, 85 patients were alive (survivors) and 110 died (nonsurvivors). HSP70 (measured by ELISA in the serum) was elevated in nonsurvivors, compared with survivors (0.39 [0.27-0.59] vs. 0.30 [0.24-0.43] ng/ml, respectively, p = 0.0101). In Kaplan-Meier survival analysis higher HSP70 levels above median were associated with a significantly increased mortality. In multivariable survival models, we show that HSP70 level above the median is an age-, sex-, body mass index-, creatinine-, and NT-proBNP-independent predictor of 5-year mortality in HF. Extracellular HSP70 could prove useful for estimating survival in patients with HF