Long non-coding RNA BANCR promotes interferon-ß-induced cardiomyocyte apoptosis by targeting signal transducer and activator of transcription 1 in vitro.

Myocardium functions as an immune organ, and myocardial ischemia-reperfusion (I/R) is known to initiate myocardial innate immune response to induce myocardial injury. However, the mechanisms underlying interferon-ß (IFN-ß)-mediated myocardial injury during I/R and whether long non-coding RNAs (lncRNAs) are involved in IFN-ß-mediated myocardial injury remain unknown. This study identified that I/R significantly induced IFN-ß expression in induced pluripotent stem cell-derived cardiomyocytes, and IFN-ß further enhanced I/R-induced myocardial apoptosis. Furthermore, it was demonstrated that the lncRNA BRAF-activated non-coding RNA (BANCR) was highly expressed in cardiomyocytes, and BANCR-knockdown suppressed signal transducer and activator of transcription 1 (STAT1) phosphorylation and IFN-ß-induced cardiomyocyte apoptosis. Furthermore, it was identified that BANCR specifically interacted with STAT1 to promote IFN-ß-STAT1 signaling and enhanced the expression of pro-apoptotic interferon stimulated genes. Overall, the present study reports that lncRNA BANCR promotes IFN-ß-mediated cardiomyocyte apoptosis following I/R injury by interacting with STAT1, suggesting lncRNA BANCR is involved in IFN-ß-induced cardiomyocyte apoptosis.

YB1 protects cardiac myocytes against H2O2­induced injury via suppression of PIAS3 mRNA and phosphorylation of STAT3.

Oxidative stress serves important roles in cardiac injury during the process of ischemia/reperfusion (I/R). Y­box protein 1 (YB1), a member of the highly conserved Y­box protein family, is closely associated with inflammation and stress responses by regulating gene transcription, RNA splicing and mRNA translation. However, the roles of YB1 in oxidative stress­induced myocardial­I/R (M­I/R) injury are unknown. The aim of the present study was to examine the effects of YB1 on H2O2­induced cardiomyocyte injury and its underlying mechanism. The results demonstrated that YB1 expression was upregulated during H2O2­induced myocardial injury. YB1 knockdown through transfection of small interfering RNA significantly aggravated cardiac cell apoptosis. Furthermore, YB1 knockdown significantly reversed the H2O2­mediated increase in phosphorylated signal transducer and activator of transcription (STAT)3, but did not affect the phosphorylation of P38, extracellular signal­regulated kinases 1/2, c­Jun N­terminal kinases, P65, Janus kinase 1 and 2 or STAT1. Moreover, protein co­immunoprecipitation and RNA­binding protein immunoprecipitation assays revealed that YB1 interacted with protein inhibitor of activated STAT 3 (PIAS3) mRNA but not its translated protein. YB1 overexpression may have promoted PIAS3 mRNA decay, decreasing PIAS3 protein levels, and therefore increased the levels of phosphorylated STAT3. Finally, YB1 knockdown, mediated by a lentivirus carrying YB1 targeted short hairpin RNA, significantly decreased left ventricle percentage fractional shortening and ejection fraction values, while increasing the infarct sizes in a rat model of M­I/R injury. These results demonstrated for the first time (to the best of our knowledge) that YB1 may protect cardiac myocytes against H2O2 or M­I/R­induced injury by binding to PIAS3 mRNA and resulting in the phosphorylation of STAT3.

Therapeutic effects of different Atorvastatin doses on vulnerable plaques in coronary arteries assessed by intracoronary optical coherence tomography.

The aim of this study was to evaluate optical coherence tomography (OCT) as an assessment of the efficacy of atorvastatin treatment.Twenty-four acute coronary syndrome (ACS) patients were allocated to conventional-dose (20 mg atorvastatin, n = 12) and intensive-dose (40-80 mg atorvastatin, n = 12) groups and correlations between changes in the OCT measurements and blood routine indexes were analyzed 9 months post-percutaneous coronary intervention (PCI).Treatment with atorvastatin resulted in a significant increase in the target thin cap fibroatheroma (TCFA) fibrous cap thicknesses in both groups. The increase was bigger in the intensive-dose group than in the conventional-dose group (184.1 ±â€Š57.4 µm vs. 125.1 ±â€Š28.6, P = .005). The TCFA lipid core arc in both groups was significantly decreased compared with baseline (72.9 ±â€Š29.3 vs. 127.6 ±â€Š50.8, P < .01 and 74.6 ±â€Š32.9 vs. 132.6 ±â€Š51.3, P < .01, respectively). Correlation analyses showed an inverse relationship between low-density lipoprotein cholesterol (LDL-c) levels and the TCFA cap thickness, and a direct relationship between C-reactive protein (CRP) level and lipid core arc.Statins significantly increased the TCFA fibrous cap thickness and reduced the lipid core arc, and OCT measurements accurately reflected the levels of blood LDL-c and CRP. TRIAL REGISTRATION: (Chinese Clinical Trial Registry) ChiCTR-IPR-17010874.

High-dose atorvastatin reloading before percutaneous coronary intervention increased circulating endothelial progenitor cells and reduced inflammatory cytokine expression during the perioperative period.

OBJECTIVE: We investigated atorvastatin reloading effects on endothelial progenitor cell (EPC) count and inflammatory cytokine expression after percutaneous coronary intervention (PCI) in patients with stable angina pectoris who had previously received long-term statin treatments. METHODS: Patients with stable angina pectoris were treated with 80 mg atorvastatin 12 hours and 40 mg atorvastatin 2 hours before coronary angioplasty (n = 15) or preoperatively with 40 mg/d atorvastatin for 7 days (n = 15) or did not receive atorvastatin (n = 15). CD45-/133+/34+, CD45-/CD34+/kinase insert domain receptor (KDR)+, and CD45-/CD144+/KDR+ EPCs in the peripheral blood were determined by flow cytometry 1 hour before as well as 1 hour, 6 hours, and 24 hours after PCI. Soluble intercellular adhesion molecule 1 (sICAM-1), hypersensitive C-reactive protein (hCRP), and troponin-I (TnI) serum concentrations were analyzed immediately prior to and 24 hours after PCI. RESULTS: In the 40mg Atorvastatin and control groups, none of the analyzed EPC blood concentrations changed significantly from 1h before operation to 1h and 6 h postoperative values. In contrast, the number of circulating early differentiation stage EPCs CD45-/133+/34+ and CD45-/CD34+/ KDR+ raised significantly from 1 h preoperative values (57.3±9.3; 57.3 ± 10.7) to 1 h postoperative ((74.4 ± 11.4; 78.8 ± 16.2), (p < 0.05)) and 6 h postoperative ((93 ± 16.9; 99.7 ± 11.9), (p < 0.05)) concentrations after coronary angioplasty in the 80mg Atorvastatin medication patients. In the control group, the sICAM-1 (174.55 ± 38.91 vs 204.11 ± 58.24) and hCRP (1.89 ± 1.93 vs 9.0 ± 11.1) serum concentrations at 24 hours after PCI were significantly elevated (P < .05) compared to preoperative values, whereas the increases in the 2 groups treated with atorvastatin were not significant. In addition, the rise in serum TnI concentration level from pre- to postoperative in the 80-mg (0.02 ± 0.02 vs 0.09 ± 0.08) and the 40-mg (0.01 ± 0.03 vs 1.2 ± 2.59) reloading groups was less than that of the controls (0.01 ± 0.02 vs 1.75 ± 3.09) (p < 0.05). CONCLUSION: Our results suggested that high-dose atorvastatin application before PCI triggered early EPC circulation. Furthermore, postoperative inflammatory cytokine sICAM-1 as well as hCRP serum levels were reduced, while postinterventional myocardial injury marker TnI elevations were inversely correlated with statin reloadings.