No abstract

We assessed the predictive ability of circulating biomarkers involved in collagen synthesis (procollagen type I N-terminal propeptide [PINP], and procollagen type III N-terminal propeptide [PIIINP], collagen degradation (c-terminal telopeptide of collagen type I [CTx] and mediators of cardiac fibrosis (Galectin-3 and soluble suppression of tumorigenicity 2 protein or sST2) as prognosis markers in 182 subjects with chronic heart failure (HF). In univariate analysis, all markers predicted mortality (except for PINP). A multivariate baseline model was fitted including variables potentially associated with mortality in HF patients. The baseline regression model included age, clinical data and biomarkers. We created four models from the baseline model augmented with the levels of hs-cTnT, CRP and NT-proBNP (model 1), CTx/PIIINP ratio, sST2 and Galectine-3 (model 2), NT-proBNP and sST2 (model 3) and NT-proBNP, CTx/PIIINP ratio and sST2 (model 4), to test whether these biomarkers have an incremental value for predicting mortality. After the addition of all biomarkers to the baseline model, age, CTx/PIIINP ratio and sST2 remained significant predictors. By contrast, Galectin-3 was not significantly associated with mortality. A multimarker strategy, demonstrated that the greatest prognostic improvement was attained with the combined addition of CTx/PIIINP ratio and sST2 highlighting the potential role of fibrosis pathways in risk stratification.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies. Antibodies against Ficolin-3 were previously identified in the sera of some SLE patients, but their prevalence and significance have not been yet investigated. The aims of this study were to determine the prevalence of anti-ficolin-3 antibodies among SLE patients and to investigate their potential as diagnostic and/or prognostic biomarkers in SLE. In this retrospective study, sera from SLE patients (n = 165) were selected from a preexisting declared biological collection. Samples from healthy controls (n = 48) were matched with SLE sera. Disease activity was determined according to the SLEDAI score. Anti-ficolin-3, anti-dsDNA and anti-C1q antibodies levels were measured in sera by ELISA. First, a highly significant difference was found in the anti-ficolin-3 levels between SLE patients and healthy subjects. Anti-ficolin-3 antibodies were detected as positive in 56 of 165 (34%) SLE patients. The titer of anti-ficolin-3 antibodies was correlated with the SLEDAI score (r = 0.38, p<0.0001). The presence of anti-ficolin-3 antibodies was associated with anti-C1q and anti-dsDNA antibodies. Regarding associations with clinical manifestations, the presence of active lupus nephritis was significantly associated with the presence of anti-ficolin-3 antibodies (p≤0.001). This association with renal involvement was higher with anti-ficolin-3 or anti-C1q antibodies than with other auto-antibodies. Interestingly, the combination of anti-ficolin-3 and anti-C1q antibodies demonstrated higher specificity than any other serological biomarker. These results suggest that anti-ficolin-3 antibodies could be useful for the diagnosis of active nephritis in SLE patients.

Heart failure is the most frequent cardiac complication of chronic kidney disease (CKD). Biomarkers help identify high-risk patients. Natriuretic peptides (BNP and NT-proBNP) are largely used for monitoring patients with cardiac failure but are highly dependent on glomerular filtration rate (GFR). Soluble suppression of tumorigenicity 2 (sST2) biomarker is well identified in risk stratification of cardiovascular (CV) events in heart failure. Furthermore, sST2 is included in a bioclinical score to stratify mortality risk. The aims of this study were to evaluate (i) the interest of circulating sST2 level in heart dysfunction and (ii) the bioclinical score (Barcelona Bio-Heart Failure risk calculator) to predict the risk of composite outcome (major adverse coronary events) and mortality in the CKD population. A retrospective study was carried out on 218 CKD patients enrolled from 2004 to 2015 at Montpellier University Hospital. sST2 was measured by ELISA (Presage ST2® kit). GFR was estimated by the CKD-EPI equation (eGFR). Indices of cardiac parameters were performed by cardiac echography. No patient had reduced ejection fraction. 112 patients had left ventricular hypertrophy, and 184 presented cardiac dysfunction, with structural, functional abnormalities or both. sST2 was independent of age and eGFR (ρ = 0.05, p = 0.44, and ρ = −0.07, p = 0.3, respectively). Regarding echocardiogram data, sST2 was correlated with left ventricular mass index (ρ = 0.16, p = 0.02), left atrial diameter (ρ = 0.14, p = 0.04), and volume index (ρ = 0.13, p = 0.05). sST2 alone did not change risk prediction of death and/or CV events compared to natriuretic peptides. Included in the Barcelona Bio-Heart Failure (BCN Bio-HF) score, sST2 added value and better stratified the risk of CV events and/or death in CKD patients (p < 0.0001). To conclude, sST2 was associated with cardiac remodeling independently of eGFR, unlike other cardiac biomarkers. Added to the BCN Bio-HF score, the risk stratification of death and/or CV events in nondialyzed CKD patients was highly improved.

Aims: Microvascular alterations occurring after myocardial infarction (MI) may represent a risk factor for multi-organ failure. Here we used in vivo photoacoustic (PA) imaging to track and define the changes in vascular oxygen saturation (sO2) occurring over time after experimental MI in multiple peripheral organs and in the brain.Methods and Results: Experimental MI was obtained in BALB/c mice by permanent ligation of the left anterior descending artery. PA imaging (Vevo LAZR-X) allowed tracking mouse-specific sO2 kinetics in the cardiac left ventricular (LV) anterior wall, brain, kidney, and liver at 4 h, 1 day, and 7 days post-MI. Here we reported a correlation between LV sO2 and longitudinal anterior myocardial strain after MI (r = −0.44, p &lt; 0.0001, n = 96). Acute LV dysfunction was associated with global hypoxia, specifically a decrease in sO2 level in the brain (−5.9%), kidney (−6.4%), and liver (−7.3%) at 4 and 24 h post-MI. Concomitantly, a preliminary examination of capillary NG2DsRed pericytes indicated cell rarefication in the heart and kidney. While the cardiac tissue was persistently impacted, sO2 levels returned to pre-MI levels in the brain and in peripheral organs 7 days after MI.Conclusions: Collectively, our data indicate that experimental MI elicits precise trajectories of vascular hypoxia in peripheral organs and in the brain. PA imaging enabled the synchronous tracking of oxygenation in multiple organs and occurring post-MI, potentially enabling a translational diagnostic modality for the identification of vascular modifications in this disease setting.

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

The screening of skeletal muscle diseases constitutes an unresolved challenge. Currently, exercise tests or plasmatic tests alone have shown limited performance in the screening of subjects with an increased risk of muscle oxidative metabolism impairment. Intensity-adjusted energy substrate levels of lactate (La), pyruvate (Pyr), β-hydroxybutyrate (BOH) and acetoacetate (AA) during a cardiopulmonary exercise test (CPET) could constitute alternative valid biomarkers to select “at-risk” patients, requiring the gold-standard diagnosis procedure through muscle biopsy. Thus, we aimed to test: 1) the validity of the V’O2-adjusted La, Pyr, BOH and AA during a CPET for the assessment of the muscle oxidative metabolism (exercise and mitochondrial respiration parameters); and 2) the discriminative value of the V’O2-adjusted energy and redox markers, as well as five other V’O2-adjusted TCA cycle-related metabolites, between healthy subjects, subjects with muscle complaints and muscle disease patients. Two hundred and thirty subjects with muscle complaints without diagnosis, nine patients with a diagnosed muscle disease and ten healthy subjects performed a CPET with blood assessments at rest, at the estimated 1st ventilatory threshold and at the maximal intensity. Twelve subjects with muscle complaints presenting a severe alteration of their profile underwent a muscle biopsy. The V’O2-adjusted plasma levels of La, Pyr, BOH and AA, and their respective ratios showed significant correlations with functional and muscle fiber mitochondrial respiration parameters. Differences in exercise V’O2-adjusted La/Pyr, BOH, AA and BOH/AA were observed between healthy subjects, subjects with muscle complaints without diagnosis and muscle disease patients. The energy substrate and redox blood profile of complaining subjects with severe exercise intolerance matched the blood profile of muscle disease patients. Adding five tricarboxylic acid cycle intermediates did not improve the discriminative value of the intensity-adjusted energy and redox markers. The V’O2-adjusted La, Pyr, BOH, AA and their respective ratios constitute valid muscle biomarkers that reveal similar blunted adaptations in muscle disease patients and in subjects with muscle complaints and severe exercise intolerance. A targeted metabolomic approach to improve the screening of “at-risk” patients is discussed.

No abstract