ATF3 coordinates the survival and proliferation of cardiac macrophages and protects against ischemia-reperfusion injury.

Cardiac resident MerTK+ macrophages exert multiple protective roles after ischemic injury; however, the mechanisms regulating their fate are not fully understood. In the present study, we show that the GAS6-inducible transcription factor, activating transcription factor 3 (ATF3), prevents apoptosis of MerTK+ macrophages after ischemia-reperfusion (IR) injury by repressing the transcription of multiple genes involved in type I interferon expression (Ifih1 and Ifnb1) and apoptosis (Apaf1). Mice lacking ATF3 in cardiac macrophages or myeloid cells showed excessive loss of MerTK+ cardiac macrophages, poor angiogenesis and worse heart dysfunction after IR, which were rescued by the transfer of MerTK+ cardiac macrophages. GAS6 administration improved cardiac repair in an ATF3-dependent manner. Finally, we showed a negative association of GAS6 and ATF3 expression with the risk of major adverse cardiac events in patients with ischemic heart disease. These results indicate that the GAS6-ATF3 axis has a protective role against IR injury by regulating MerTK+ cardiac macrophage survival and/or proliferation.

Elevated tissue inhibitor of metalloproteinase-1 along with left atrium hypertrophy predict atrial fibrillation recurrence after catheter ablation.

This study aimed to establish a model that predicts atrial fibrillation (AF) recurrence after catheter ablation using clinical risk factors and biomarkers. We used a prospective cohort study, including 230 consecutive persistent AF patients successfully treated with catheter ablation from January 2019 to December 2020 in our hospital. AF recurrence was followed-up after catheter ablation, and clinical risk factors and biomarkers for AF recurrence were analyzed. AF recurred after radiofrequency ablation in 72 (31%) patients. Multiple multivariate logistic regression analysis demonstrated that tissue inhibitor of metalloproteinase-1 (TIMP-1) and left atrium diameter (LAd) were closely associated with AF recurrence. The prediction model constructed by combining TIMP-1 and LAd effectively predicted AF recurrence. Additionally, the model's performance discrimination, accuracy, and calibration were confirmed through internal validation using bootstrap resampling (1,000 times). The model showed good fitting (Hosmer-Lemeshow goodness chi-square 3.76138, p = 0.926) and had a superior discrimination ability (the area under the receiver operation characteristic curve0.917; 95% CI 0.882-0.952). The calibration curve showed good agreement between the predicted probability and the actual probability. Moreover, the decision curve analysis (DCA) showed the clinical useful of the nomogram. In conclusion, our predictive model based on serum TIMP-1 and LAd levels could predict AF recurrence after catheter ablation.

Higher Serum Lysophosphatidic Acids Predict Left Ventricular Reverse Remodeling in Pediatric Dilated Cardiomyopathy.

Background: The prognosis of pediatric dilated cardiomyopathy (PDCM) is highly variable, ranging from death to cardiac function recovery. Left ventricular reverse remodeling (LVRR) represents a favorable prognosis in PDCM. Disturbance of lipid metabolism is associated with the change of cardiac function, but no studies have examined lipidomics data and LVRR. Methods: Discovery analyses were based on 540 targeted lipids in an observational, prospective China-AOCC (An Integrative-Omics Study of Cardiomyopathy Patients for Diagnosis and Prognosis in China) study. The OPLS-DA and random forest (RF) analysis were used to screen the candidate lipids. Associations of the candidate lipids were examined in Cox proportional hazards regression models. Furthermore, we developed a risk score comprising the significant lipids, with each attributed a score of 1 when the concentration was above the median. All significant findings were replicated in a validation set of the China-AOCC study. Results: There were 59 patients in the discovery set and 24 patients in the validation set. LVRR was observed in 27 patients (32.5%). After adjusting for age, left ventricular ejection fraction (LVEF), and left ventricular end-diastolic dimension (LVEDD) z-score, lysophosphatidic acids (LysoPA) 16:0, LysoPA 18:2, LysoPA 18:1, and LysoPA 18:0 were significantly associated with LVRR in the discovery set, and hazard ratios (HRs) were 2.793 (95% CI, 1.545-5.048), 2.812 (95% CI, 1.542-5.128), 2.831 (95% CI, 1.555-5.154), and 2.782 (95% CI, 1.548-5.002), respectively. We developed a LysoPA score comprising the four LysoPA. When the LysoPA score reached 4, LVRR was more likely to be observed in both sets. The AUC increased with the addition of the LysoPA score to the LVEDD z-score (from 0.693 to 0.875 in the discovery set, from 0.708 to 0.854 in the validation set) for prediction of LVRR. Conclusions: Serum LysoPA can predict LVRR in PDCM patients. When the LysoPA score was combined with the LVEDD z-score, it may help in ascertaining the prognosis and monitoring effects of anti-heart failure pharmacotherapy.

Biofilm formation in Acinetobacter baumannii was inhibited by PAßN while it had no association with antibiotic resistance.

This study was conducted to investigate the relationship between Acinetobacter baumannii biofilm formation and antibiotic resistance. Furthermore, the effects of PAßN, a potential efflux pump inhibitor, on A. baumannii biofilm formation and dispersion were tested, and the gene expression levels of efflux pumps were determined to study the mechanisms. A total of 92 A. baumannii isolates from infected patients were collected and identified by multiplex PCR. The antimicrobial susceptibility of A. baumannii clinical isolates was tested by VITEK 2 COMPACT® . Genotypes were determined by ERIC-2 PCR. Biofilm formation and dispersion were detected by crystal violet staining. The presence and mRNA expression of efflux pump genes were analyzed by conventional PCR and real-time PCR, respectively. More than 50% of the A. baumannii strains formed biofilm and were divided into different groups according to their biofilm-forming ability. Antibiotic resistance rates among most groups did not significantly differ. There were 7 clonal groups in 92 strains of A. baumannii and no dominant clones among the different biofilm-forming groups. PAßN inhibited A. baumannii biofilm formation and enhanced its dispersion, whereas adeB, adeJ, and adeG and the mRNA expression of adeB, abeM, and amvA showed no differences in the different biofilm-forming groups. In conclusion, there was no clear relationship between biofilm formation and antibiotic resistance in A. baumannii. The effects of PAßN on A. baumannii biofilm formation and dispersion were independent of the efflux pumps.

Association of Soluble ST2 Serum Levels With Outcomes in Pediatric Dilated Cardiomyopathy.

BACKGROUND: Prognosis in patients with pediatric dilated cardiomyopathy (PDCM) is urgently required to identify high-risk patients. Elevated soluble ST2 (sST2) is associated with prognosis in adult patients with heart failure. This study aimed to assess the prognostic value of sST2 in PDCM. METHODS: Ninety-four patients with PDCM were enrolled after admission from 2 centres in China and followed up for adverse events (death, cardiac transplantation, and heart-failure-related rehospitalization). B-type natriuretic peptide (BNP) and sST2 levels were measured. RESULTS: Over a median of 678 (interquartile range [IQR]: 533-785) days, 28 (29.8%) adverse events occurred. Patients in the highest tertile of sST2 levels had increased risk of short-term (< 6 months) (adjusted hazard ratio [HR]: 8.36, 95% confidence interval [CI], 1.02-73.52; P < 0.05) and long-term adverse events (2 years) (adjusted HR: 4.23; 95% CI, 1.32-13.60; P < 0.01) than those in lower tertiles. The C-statistic was increased with addition of sST2 to BNP from 0.697 (95% CI, 0.541-0.852) to 0.812 (95% CI, 0.697-0.939) for short-term and from 0.712 (95% CI, 0.604-0.819) to 0.798 (95% CI, 0.697-0.899) for prediction of long-term adverse events. An intermediate-risk subgroup was identified, and 24% had adverse events. When serial measurements were taken in a nested case-control subgroup, sST2 levels were constantly high in patients with late adverse events (> 6 months) but gradually decreased in nonadverse-event controls compared with 3-month and 6-month baseline levels. CONCLUSIONS: In patients with PDCM, serum sST2 levels are associated with adverse events and have robust prognostic value. Serial measurements of sST2 could help in managing patients for monitoring outcomes of treatment.