A long noncoding RNA CHAIR protects the heart from pathological stress.

Mammalian genomes have been found to be extensively transcribed. In addition to classic protein coding genes, a large numbers of long noncoding genes (lncRNAs) have been identified, while their functions, especially in heart diseases, remain to be established. We hypothesized that heart failure progression is controlled by tissue-specific lncRNAs. In the present study, we found that the cardiac-enriched lncRNA 4632428C04Rik, named as cardiomyocyte hypertrophic associated inhibitory RNA (CHAIR), is dynamically regulated during heart development, is expressed at low levels in embryonic hearts and accumulated at high levels in adult hearts. More interestingly, the lncRNA was down-regulated during cardiac hypertrophy and failure both in mice and humans. Importantly, loss of lncRNA CHAIR has no effects on normal hearts, whereas it results in accelerated heart function decline, increased hypertrophy, and exacerbated heart failure in response to stress. In contrast, restoring the expression of lncRNA CHAIR rescued the hearts from hypertrophy and failure. DNMT3A was recruited to CHAIR promoter during heart failure to suppress its expression. Reciprocally, CHAIR interacted with DNMT3A to inhibit its DNA-binding activity. Taken together, our data revealed a new cardioprotective lncRNA that represses heart failure through an epigenetic mechanism.

Prognostic value of fractalkine/CX3CL1 concentration in patients with acute myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Recent studies demonstrated that fractalkine (FKN) is critically involved in the regulation of inflammation and cardiac function. OBJECTIVE: This study aimed to investigate the prognostic value of circulating FKN in patients with ST-elevated acute myocardial infarction (STEMI) after primary PCI. METHODS: We enrolled ninety consecutive STEMI patients and investigated the association of circulating FKN with myocardial salvage and the occurrence of major adverse cardiac events (MACE) after PCI. RESULTS: During a median follow-up of 387 days, total 15 MACE (16.67%) were registered in the study population. Patients with MACE were more likely to be occurred in elderly patients with 3-vessel disease. Correlation analysis demonstrated the level of FKN at day 1 after PCI (FKN@day-1) not only significantly correlated with the levels of hs-TnT at day 7 after PCI (R2 = 0.06; p = 0.02) but inversely correlated with the measurements of LVEF at 1-month observation (R2 = 0.10; p = 0.00). Kaplan-Meier survival analyses further revealed that patients with the level of FKN@day-1 above the median had a higher incidence of MACE compared with those whose FKN@day-1 levels below the median (log-rank test x2 = 13.29, p < 0.001). In addition, multivariate Cox regression analysis demonstrated that FKN@day-1 was an independent predictor of MACE (hazard ratio: 4.63; 95% confidence interval: 1.53-14.01; p = 0.00), together with WBC count and 3-vessel disease for STEMI patients. CONCLUSIONS: Our study demonstrates that FKN@day-1 is negative correlated with myocardial salvage after acute myocardial infarction and might be a valuable prognostic marker of MACE in patients with STEMI undergone PCI.

Monomeric CRP Aggravates Myocardial Injury After Myocardial Infarction by Polarizing the Macrophage to Pro-Inflammatory Phenotype Through JNK Signaling Pathway.

OBJECTIVE: A polarized macrophage response plays a critical role in the pathophysiological process of myocardial infarction (MI). Several studies have shown a pro-inflammatory role for monomeric C-reactive protein (mCRP) in cardiovascular disease. However, the mechanism of how mCRP regulates macrophage phenotype switching remains unknown. In the present study, the effect of mCRP on macrophage polarization and its pathological function in myocardial repair after myocardial infarction was investigated. METHODS: MI was induced by permanent ligation of the left anterior descending coronary artery in ICR mice. Adult mice were injected with mCRP (2.5 mg/kg) with or without SP600125 (15 mg/kg, JNK inhibitor) 45 min before MI. The cardiac function, scar size as well as cardiac fibrosis, infiltration of inflammatory cells, and the level of proteins in the JNK signaling pathway in infarcted myocardium were assessed. In addition, the phenotypic characterization of macrophages was further measured by ELISA, flow cytometry and quantitative RT-PCR in cultured THP-1 cells or peritoneal macrophages. RESULTS: Cardiac function deterioration, ventricular dilatation and fibrosis were exacerbated in mice pretreatment with mCRP following MI. Meanwhile, an increased accumulation of infiltrated inflammatory cells in infarcted myocardium was observed in the mCRP group. Moreover, activation of the JNK signaling pathway was markedly elevated in mCRP treated animals post-MI. In contrast, pharmacological inhibition of JNK phosphorylation activity by SP600125 muted the detrimental effects of mCRP in MI mice. Furthermore, in vitro and in vivo co-culture experiments showed that mCRP shifted macrophage polarization towards pro-inflammatory phenotypes, and this polarization could be abolished by sp600125. CONCLUSION: Taken together, our results imply that mCRP impairs myocardial repair after myocardial infarction by polarizing the macrophages into the pro-inflammatory M1 phenotype via the JNK-dependent pathway.

Incidence and Risk Factors for Antiplatelet Therapy-Related Bleeding Complications Among Elderly Patients After Coronary Stenting: A Multicenter Retrospective Observation.

Purpose: To determine the incidence and risk factors of bleeding events as well as assess the performance of the PRECISE-DAPT score in elderly patients (≥75 years) who underwent percutaneous coronary intervention (PCI) and one-year dual antiplatelet therapy (DAPT). Methods: A total of 940 patients (≥75 years) who received PCI and one-year DAPT were retrospectively enrolled into the study. The multivariable logistic regression analysis was conducted to identify risk factors of antiplatelet-related bleeding complications. The receiver operating characteristic (ROC) curve analysis and the Delong test were performed to obtain the optimized PRECISE-DAPT score. Results: It was observed that 89 (9.47%) patients suffered bleeding complications, while 37 (3.94%) of them had the Bleeding Academic Research Consortium (BARC, type ≥2) bleeding events. We stratified the PRECISE-DAPT score in tertiles (T1: ≤23; T2:24 to 32; T3: ≥33) and found that BARC ≥ 2 type bleeding occurred more frequently in T3 than in T1 and T2 (8.25 vs. 1.46% vs. 2.40%, p <0.05). The ROC curve analysis revealed that the PRECISE-DAPT score cutoff for BARC ≥2 type bleeding prediction was 33. In comparison with the current recommended cutoff score of 25 (AUC: 0.608, based on ROC analysis), the Delong test indicated significantly improved ability for predicting BARC ≥ 2 type bleeding events using the proposed cutoff value of 33, AUC of 0.676 (p = 0.03), and Brier Score of 0.04. The multivariable logistic regression analysis demonstrated that the PRECISE-DAPT score ≥ 33 [OR: 3.772; 95% CI (1.229, 11.578); p = 0.02] was associated with BARC ≥ 2 type bleeding event, along with a history of hemorrhagic stroke [OR: 6.806; 95% CI (1.465, 31.613); p = 0.014], peptic ulcer [OR: 3.871; 95% CI (1.378, 10.871); p = 0.01], and/or myocardial infarction [MI, OR: 3.081; 95% CI (1.140, 8.326); p = 0.027]. Conclusion: A higher PRECISE-DAPT score of 33 might be a more reasonable cutoff value for predicting BARC ≥2 type bleeding risk in CAD patients (≥75 years). In addition, the history of hemorrhagic stroke, peptic ulcer, and myocardial infarction were identified as the risk factors of BARC ≥2 type bleeding events.

The burden of premature ventricular contractions predicts adverse fetal and neonatal outcomes among pregnant women without structural heart disease: A prospective cohort study.

BACKGROUND: Premature ventricular contractions (PVCs) may increase during pregnancy, however, few studies have evaluated the relationship between PVCs and the pregnant outcomes. HYPOTHESIS: PVCs may increase the adverse fetal/neonatal outcomes in pregnant women. METHODS: Six thousand one hundred and forty-eight pregnant women were prospectively enrolled in our center between 2017 and 2019 in the study. The average PVC burden was determined by calculating the number of PVCs in total beats. Those who had a PVC burden >0.5% were divided into two groups based on the presence or absence of adverse fetal or neonatal events. The adverse outcomes were compared between the groups to assess the impact of PVCs on pregnancy. RESULTS: A total of 103 (1.68%) women with a PVC burden >0.5% were recorded. Among them, 17 adverse events (12 cases) were documented, which was significantly higher than that among women without PVCs (11.65% vs. 2.93%, p < .01). The median PVC burden among pregnant women with PVCs was 2.84% (1.02%-6.1%). Furthermore, compared with that of the women without adverse events, the median PVC burden of women with adverse fetal or neonatal outcomes was significantly higher (9.02% vs. 2.30%, p < .01). Multivariate logistic regression analysis demonstrated that not the LVEF, heart rate and bigeminy, but only the PVC burden was associated with adverse fetal or neonatal outcomes among pregnant women with PVCs (OR: 1.34, 95% CI [1.11-1.61], p < .01). CONCLUSIONS: Frequent PVCs have adverse effects on pregnancy, and the PVC burden might be an important factor associated with adverse fetal and neonatal outcomes among pregnant women with PVCs.