RESUMEN
Recovery of cardiac function is the holy grail of heart failure therapy yet is infrequently observed and remains poorly understood. In this study, we performed single-nucleus RNA sequencing from patients with heart failure who recovered left ventricular systolic function after left ventricular assist device implantation, patients who did not recover and non-diseased donors. We identified cell-specific transcriptional signatures of recovery, most prominently in macrophages and fibroblasts. Within these cell types, inflammatory signatures were negative predictors of recovery, and downregulation of RUNX1 was associated with recovery. In silico perturbation of RUNX1 in macrophages and fibroblasts recapitulated the transcriptional state of recovery. Cardiac recovery mediated by BET inhibition in mice led to decreased macrophage and fibroblast Runx1 expression and diminished chromatin accessibility within a Runx1 intronic peak and acquisition of human recovery signatures. These findings suggest that cardiac recovery is a unique biological state and identify RUNX1 as a possible therapeutic target to facilitate cardiac recovery.
RESUMEN
OBJECTIVE: To comprehensively characterize the DNA virome in semen samples collected for in vitro fertilization (IVF). DESIGN: A descriptive clinical study. SETTING: Single academic fertility center. PATIENT(S): Twenty-four male partners from couples undergoing IVF. INTERVENTION(S): Couples were randomized to receive 1 g of azithromycin (standard of care) or no azithromycin at the time of baseline IVF assessment. Semen samples were collected at the time of the female partners' egg retrieval, and 100 µL of the sample was used for the virome analysis. MAIN OUTCOME MEASURE(S): Detection of viruses by ViroCap enrichment of viral nucleic acid and sequencing. Association between the virome, semen parameters, and pregnancy outcomes. RESULT(S): We detected viruses in 58% of the participants. Viruses included polyomaviruses, papillomaviruses, herpesviruses, and anelloviruses. Viromes detected in semen had little overlap with the viromes detected in vaginal samples from their female partners collected at the time of embryo transfer, which were analyzed in a previous study. A lower viral diversity in semen samples was positively associated with pregnancy (Hodges-Lehmann estimate of difference, 1; 95% confidence interval, 2-0.00003). There was no association between viral diversity and sperm concentration, motility, or fertilization rates. CONCLUSION(S): This comprehensive characterization of the DNA virome in semen reveals an association between virome diversity and pregnancy in couples undergoing IVF. However, no association was found with specific semen parameters or fertilization rates, suggesting that viral exposure may negatively affect pregnancy after fertilization. Future studies should be undertaken to evaluate the associations between the semen virome with IVF outcomes in larger cohorts.
