Benefits of early administration of Sacubitril/Valsartan in patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention.

OBJECTIVE: To evaluate the effects of early administration of Sacubitril/Valsartan (Sac/Val) in patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention (pPCI). METHODS: This prospective, controlled, single-center study randomized 186 ST-segment elevation myocardial infarction patients to one of the following two groups: Sac/Val group: early administration of Sac/Val within 24 hours after pPCI; control group: conventional angiotensin-converting enzyme inhibitors (ACEI) application. The creatine Kinase (CK) peak after the surgery, the incidence of acute heart failure during hospitalization, level of NT-proBNP and left ventricular ejection fraction (LVEF) measured by ultrasound before discharge and soluble suppression of tumorigenicity2 (sST2), LVEF, infarct size determined by single photon emission computed tomography (SPECT), readmission rate within 6 months were recorded and compared between two groups. RESULTS: Compared to the control group, Sac/Val could decrease the CK peak and the incidence of acute heart failure after pPCI; the level of NT-proBNP was lower and LVEF was higher before discharge in the Sac/Val group. After 6 months, the patients who had taken Sac/Val had a higher LVEF, a smaller infarct size determined by SPECT, lower sST2 and readmission rate. CONCLUSION: Patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention could benefit from early administration of Sacubitril/Valsartan, the effect was superior to conventional ACEI.

Downregulation of DEC1 by RNA interference attenuates ischemia/reperfusion-induced myocardial inflammation by inhibiting the TLR4/NF-κB signaling pathway.

Inflammation has been implicated in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury (MIRI). Previous studies have confirmed that deleted in esophageal cancer 1 (DEC1) is an important transcription factor in inflammation. However, the role of DEC1 in MIRI remains unclear. The present study aimed to determine whether the downregulation of DEC1 by RNA interference alleviated inflammation to protect against MIRI. Adult Sprague-Dawley rats (n=48) were randomly divided into four groups: Sham; I/R; adenovirus expressing green fluorescent protein control (Ad-G-Control); and DEC1-targeting RNA interference (Ad-G-DEC1) groups. Following gene delivery 4 days later, the rat myocardial I/R model was established and myocardial enzymes [creatine kinase (CK) and lactate dehydrogenase (LDH)] were detected. Hematoxylin and eosin (H&E) staining was performed to evaluate the myocardial damage and the infarct area was assessed using Evans Blue/triphenyltetrazolium chloride staining. The inflammatory mediators interleukin (IL)-ß and tumor necrosis factor (TNF)-α were also detected using ELISA kits to assess the inflammatory response. Finally, western blotting and reverse transcription-quantitative PCR were used to analyze the expression levels of associated proteins and mRNAs. Ad-G-DEC1 RNA interference markedly decreased DEC1 expression levels. In addition, following the downregulation of DEC1 expression, the infarct size, CK, LDH, Toll-like receptor (TLR)4, NF-κB, IL-ß and TNF-α levels were all significantly decreased. In conclusion, the results of the present study suggested that the downregulation of DEC1 may decrease the inflammation by suppressing the TLR4/NF-κB signaling pathway, which may represent a therapeutic target for MIRI.

TRAF5 protects against myocardial ischemia reperfusion injury via AKT signaling.

During the processes of myocardial ischemia reperfusion (I/R) injury, inflammation and apoptosis play an important role. I/R and its induced acute myocardial infarction (AMI) with high morbidity and mortality, and there is no effective treatment for it so far. TRAF5 has been shown to regulate inflammation and apoptosis in atherosclerosis, steatosis and melanoma cells, but its function in myocardial I/R injury is still unclear. This study demonstrates that the expression of TRAF5 is significant up-regulation in heart tissues of I/R injury mice and hypoxia/reoxygenation (H/R)-stimulated cardiomyocytes. TRAF5 knockout mice exhibites heavier heart damage, inflammatory response and cell death after myocardial I/R injury. Further, TRAF5 overexpression inhibites inflammation and apoptosis of H/R-stimulated cardiomyocytes. Mechanistically, we prove that TRAF5 promotes the activation of AKT. Overall, our study indicates that TRAF5 can regulate the processes of myocardial I/R injury. TRAF5 can be a new therapy target for myocardial I/R injury.

The Diagonal Branch to the Accompanying Vein Fistula After Rotational Atherectomy.

We report a case of rotational-atherectomy induced fistula between the diagonal branch and the accompanying vein. Thus far, the patient has had no relevant symptoms; thus, no intervention has been undertaken. We will closely monitor the patient to determine future treatment.

TRAF1 Exacerbates Myocardial Ischemia Reperfusion Injury via ASK1-JNK/p38 Signaling.

Background After acute myocardial infarction, the recovery of ischemic myocardial blood flow may cause myocardial reperfusion injury, which reduces the efficacy of myocardial reperfusion. Ways to reduce and prevent myocardial ischemia/reperfusion (I/R) injury are of great clinical significance in the treatment of patients with acute myocardial infarction. TRAF1 (tumor necrosis factor receptor-associated factor 1) is an important adapter protein that is implicated in molecular events regulating immunity, inflammation, and cell death. Little is known about the role and impact of TRAF1 in myocardial I/R injury. Methods and Results TRAF1 expression is markedly induced in wild-type mice and cardiomyocytes after I/R or hypoxia/reoxygenation stimulation. I/R models were established in TRAF1 knockout mice and wild type mice (n=10 per group). We demonstrated that TRAF1 deficiency protects against myocardial I/R-induced loss of heat function, inflammation, and cardiomyocyte death. In addition, overexpression of TRAF1 in primary cardiomyocytes promotes hypoxia/reoxygenation-induced inflammation and apoptosis in vitro. Mechanistically, TRAF1 promotes myocardial I/R injury through regulating ASK1 (apoptosis signal-regulating kinase 1)-mediated JNK/p38 (c-Jun N-terminal kinase/p38) MAPK (mitogen-activated protein kinase) cascades. Conclusions Our results indicated that TRAF1 aggravates the development of myocardial I/R injury by enhancing the activation of ASK1-mediated JNK/p38 cascades. Targeting the TRAF1-ASK1-JNK/p38 pathway provide feasible therapies for cardiac I/R injury.

Serum glycated albumin is superior to hemoglobin A1c for correlating with HMGB1 in coronary artery disease with type 2 diabetic mellitus patients.

High mobility group box 1 protein (HMGB1) was significantly increased in coronary artery disease (CAD) with type 2 diabetic mellitus (T2DM) patients. This study was to investigate the relationship between average blood glucose level and HMGB1 level in CAD with T2DM patients. 164 CAD patients were divided into two groups: CAD with T2DM patients group and CAD without T2DM patients group. Glycated albumin (GA) and glycosylated hemoglobin A1c (HbA1c) and HMGB1 concentrations were measured in CAD with T2DM patients. The fasting glucose levels, GA and HbA1c levels were sinificantly increased in CAD with T2DM patients compared to those in CAD without T2DM patients (all P<0.05). The hs-CRP levels in CAD with T2DM patients were significantly higher than those in CAD without T2DM patients (P<0.05). The HMGB1 levels in CAD with T2DM patients were also significantly higher than those in CAD without T2DM patients (P<0.05). Both serum GA levels and HbA1c levels were positively correlated with HMGB1 levels (n=84, r=0.512 and r=0.402, both P<0.05). The present study showed that both serum GA levels and HbA1c levels were positively related with HMGB1 levels in CAD with T2DM patients. Increased blood glucose levels may contribute to the increased HMGB1 levels. GA level is superior to HbA1c level for correlating with HMGB1 level.

Atorvastatin reduces serum HMGB1 levels in patients with hyperlipidemia.

High mobility group box 1 protein (HMGB1) has been identified as a novel pro-inflammatory cytokine in coronary artery disease. This study investigated the effect of atorvastatin on serum HMGB1 levels in patients with hyperlipidemia. In 72 patients with hyperlipidemia, serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP) were compared with the levels in 32 control patients. In hyperlipidemic patients, serum HMGB1 levels were also determined by ELISA before and after a 3-month treatment of atorvastatin (20 mg/day). TC and LDL-C levels in the hyperlipidemic group (6.37±0.94 and 4.99±0.75 mmol/l, respectively) were significantly higher compared to those in the control group (4.34±0.89 and 2.57±0.82 mmol/l, respectively) (both P<0.05). Hs-CRP and HMGB1 levels in the hyperlipidemic group (3.91±1.06 mg/l and 5.42±1.56 ng/ml, respectively) were also significantly higher compared to those in the control group (1.53±0.45 mg/l and 2.11±0.95 ng/ml, respectively) (both P<0.05). After treatment with atorvasatin for three months, TC and LDL-C levels in the hyperlipidemic group were significantly decreased compared to those prior to treatment (TC, 4.67±0.89 vs. 6.37±0.94 mmol/l and LDL-C, 2.75±0.92 vs. 4.99±0.75 mmol/l, respectively) (both P<0.05). HMGB1 and hs-CRP levels in the hyperlipidemic group (3.07±1.24 ng/ml and 1.87±0.79 mg/l, respectively) were also significantly decreased compared to levels prior to treatment (5.42±1.56 ng/ml and 3.91±1.06 mg/l, respectively) (both P<0.05). Serum HMGB1 levels are increased in patients with hyperlipidemia which could be reduced by atorvastatin.

Increased serum interleukin-34 in patients with coronary artery disease.

OBJECTIVE: This study investigated levels of interleukin (IL)-34, a proinflammatory cytokine, in patients with coronary artery disease (CAD). METHODS: Following coronary artery angiography, 91 patients with CAD (including stable and unstable angina pectoris) were divided into two groups, the CAD group (coronary artery stenosis ≥ 50%) and the control group (coronary artery stenosis < 50%). Serum levels of factors including IL-34 and high sensitivity C-reactive protein (hs-CRP) were measured. RESULTS: IL-34 and hs-CRP levels were significantly higher in the CAD group than in the control group (191.3 ± 17.9 pg/ml versus 125.4 ± 14.8 pg/ml and 3.08 ± 1.81 mg/ml versus 1.42 ± 1.01 mg/ml, respectively), with a significantly positive correlation between IL-34 and hs-CRP levels in the CAD group. Multiple regression analysis showed that IL-34 and hs-CRP levels were independent predictors of CAD (IL-34: odds ratio [OR] 2.073, 95% confidence intervals (CI) 1.419, 2.672; hs-CRP: OR 1.878, 95% CI 1.172, 2.531). CONCLUSIONS: IL-34 levels were significantly increased in patients with CAD, and positively correlated with hs-CRP levels, suggesting that IL-34 may be an independent predictor of CAD.