Biology subjects

Mercier-Nome, F.

Publications and source records attributed to Mercier-Nome, F..

3 recordsLinked to original sources

bioRxiv2025

A cocktail of B vitamins with nicotinamide riboside, folate and cobalamin preserves cardiac function and mitochondrial oxidative capacities in a mouse model of heart failure.

Despite a substantial therapeutic arsenal to treat patients affected by heart failure (HF), no treatment specifically targets alterations of cardiac energy metabolism and mitochondrial functions. Yet, these alterations are now well-known and their involvement in HF pathophysiology has been demonstrated for years. Based on the results of previous studies demonstrating the cardiac preventive effects of B vitamins when introduced before inducing cardiac pressure overload in mice, we investigated the efficacy of a diet supplemented with a B vitamin cocktail (B3, B9 and B12 (3VitB)) to restore energy metabolism and improve cardiac function in an animal model of established HF. Heart Failure was induced by transverse aortic constriction (TAC) in male and female C57Bl6N mice and 3VitB treatment was introduced four weeks later in animals meeting criteria of heart failure with restricted ejection fraction. A 20-week survival study showed a significant longer life expectancy in TAC males treated with Vit3B in comparison with TAC males fed with normal diet, and this was associated with a reduction in the over time TAC-induced alterations of ejection fraction, stroke volume, and systolic and diastolic left ventricular diameter. Although, these effects on survival and cardiac function were less clear in females due to their higher resistance to TAC, the Vit3B cocktail was beneficial in females as 8 weeks of treatment improved physical capacities and led to milder cardiomyocyte stress-induced hypertrophy in similar ways to those observed in males. In both sexes, 3VitB treated TAC mice exhibited higher mitochondrial oxidative capacities than TAC mice fed with normal diet. This was at least partly supported by the maintenance of the mitochondrial biogenesis process activation, demonstrated by the higher expression of genes such as Tfam and NRF1 protein level in 3VitB treated TAC groups. Interestingly, our results revealed sex-specificities not only in response to cardiac pressure overload but also in response to 3VitB treatment that acted through different mechanisms that involved AMPK in males and SIRT1 in females. Overall, this study demonstrated the efficacy of 3VitB to preserved cardiac function and energy metabolism in an established HF model, especially in males that are more sensitive to cardiac pressure overload. This confers credit to vitamin supplementations and to metabolic therapy as new strategies in the treatment of HF.

physiology↗

bioRxiv2023

Cardiac gene therapy with PDE2A limits remodeling and arrhythmias in mouse models of heart failure induced by catecholamines

BACKGROUNDConstitutive cardiac PDE2 activation was shown to protect against contractile dysfunction and arrhythmia in heart failure (HF). However, it remains unknown whether an acute elevation of PDE2 is efficient to prevent maladaptive remodeling and arrhythmia. In this study we tested whether increasing acutely PDE2A activity in preclinical models of HF using cardiac PDE2 gene transfer could be of therapeutic value. METHODS AND RESULTSC57BL/6 male mice were injected with serotype 9 adeno-associated viruses (AAV9) encoding for PDE2A, or luciferase (LUC). Cardiac function assessed by echocardiography unveiled neither structural change nor dysfunction consecutive to PDE2A overexpression while AAV9 inoculation led to a {approx}10-fold rise of PDE2A protein levels. Two weeks after AAV9 injections, mice were implanted with osmotic minipumps delivering NaCl or isoproterenol (Iso) (60 mg/kg/day) or Iso and phenylephrine (Iso+Phe, 30 mg/kg/day each) for 2 weeks. In LUC mice, chronic infusion with Iso increased left ventricular (LV) weight over body weight ratio, promoted fibrosis and decreased ejection fraction, but animals overexpressing PDE2A were protected towards these deleterious effects. Similarly, concomitant treatment with Iso+Phe promoted LV contractile dysfunction, fibrosis and apoptosis in LUC mice, while PDE2A overexpression limited these adverse outcomes. Furthermore, inotropic responses to Iso of ventricular cardiomyocytes isolated from Iso+Phe-LUC mice loaded with 1 {micro}mol/L Fura-2AM and stimulated at 1 Hz to record calcium transients and sarcomere shortening were dampened. Chronic treatment with catecholamines favoured spontaneous calcium waves upon {beta}-AR stimulation at the cellular level and promoted susceptibility to ventricular arrhythmias in vivo evoked by catheter-mediated ventricular pacing after Iso and atropine injection. However, these adverse effects were blunted by the cardiac gene therapy with PDE2A. CONCLUSIONGene therapy with PDE2A limits cardiac adverse left ventricle remodeling and dysfunction induced by catecholamines as well as ventricular arrhythmias, providing evidence that acutely increasing PDE2A activity could prevent progression towards HF.

physiology↗

bioRxiv2021

The unforeseen intracellular lifestyle of Enterococcus faecalis in hepatocytes

Enterococcus faecalis is a bacterial species present at a sub-dominant level in the human gut microbiota. This commensal turns into an opportunistic pathogen under specific conditions involving dysbiosis and host immune deficiency. E. faecalis is also the only intestinal pathobiont identified to date as contributing to liver damage in alcoholic liver disease. We have previously observed that E. faecalis is internalized in hepatocytes. Here, the survival and fate of E. faecalis was examined in hepatocytes, the main epithelial cell type in the liver. Although referred to as an extracellular pathogen, we demonstrate that E. faecalis is able to survive and divide in hepatocytes, and form intracellular clusters in two distinct hepatocyte cell lines, in primary mouse hepatocytes, as well as in vivo. This novel process extends to kidney cells. Unravelling the intracellular lifestyle of E. faecalis, our findings contribute to the understanding of pathobiont-driven diseases.

microbiology↗