miRNA­504 inhibits p53­dependent vascular smooth muscle cell apoptosis and may prevent aneurysm formation.

Abdominal aortic aneurysm (AAA) is a common disease that is associated with the proliferation and apoptosis of vascular smooth muscle cells (VSMCs). VSMCs are regulated by microRNAs (miRNA). The aim of the present study was to identify miRNA sequences that regulate aortic SMCs during AAA. miRNA­504 was identified using a miRNA PCR array and by reverse transcription­quantitative polymerase chain reaction analysis, and its expression levels were observed to be downregulated in the aortic cells derived from patients with AAA when compared with controls. Transfection of SMCs with pMSCV­miRNA­504 vector was performed, and cell proliferation and the expression levels of proliferating cell nuclear antigen (PCNA), replication factor C subunit 4 (RFC4), B­cell lymphoma­2 (Bcl­2) and caspase­3/9 were measured by western blotting. The mechanisms underlying the effects of miRNA­504 was then analyzed. The results demonstrated that overexpression of miRNA­504 significantly upregulated the expression levels of PCNA, RFC4 and Bcl­2, while caspase­3/9 expression was significantly inhibited when compared with non­targeting controls. In addition, miRNA­504 overexpression was observed to promote the proliferation of SMCs. The expression level of the tumor suppressor, p53, which is known to be a direct target of miRNA­504, was inhibited following transfection of SMCs with pMSCV­miRNA­504. In addition, the expression of the downstream targets of p53, p21 and Bcl­like protein­4, were significantly reduced following overexpression of miRNA­504. These results revealed the anti­apoptotic role of miRNA­504 in SMCs derived from patients with AAA via direct targeting of p53.

The Effects of Ivabradine on Cardiac Function after Myocardial Infarction are Weaker in Diabetic Rats.

BACKGROUND/AIMS: Plasma norepinephrine (NE) and brain natriuretic peptide (BNP, termed BNP-45 in rats) are considered as essential neurohormones indicating heart failure progression. The purposes of this study were to examine the effects of ivabradine (IBD) on cardiac function and plasma NE and BNP-45 after chronic ischemic heart failure (CHF) in non-diabetic rats and diabetic rats. We further determined if sympathetic NE uptake-1 (a major pathway to metabolize NE) mechanism is responsible for the role played by IBD. METHODS: We ligated rat's coronary artery to induce CHF; and injected streptozotocin (STZ) to induce diabetic hyperglycemia. Echocardiography was employed to determine cardiac function. We used ELISA to examine plasma NE and BNP-45; and Western Blot analysis to examine the protein levels of NE uptake-1 in sympathetic nerves. RESULTS: CHF increased the levels of NE and BNP-45 in non-STZ rats and STZ rats. Systemic injection of IBD significantly attenuated the augmented NE and BNP-45 and impaired left ventricular function induced by CHF in those rats. This effect appeared to be less in STZ rats. A liner relation was observed between the NE/BNP-45 levels and left ventricular function after administration of IBD. Also, IBD was observed to have a recovery effect on the downregulated NE uptake-1 evoked by CHF, but to a smaller degree in STZ rats. CONCLUSION: Our data revealed specific signaling mechanisms by which IBD improves the cardiac function as IBD alleviates impaired NE uptake-1and thereby decreases heightened NE and BNP-45 induced by CHF. Our data also demonstrated that the effects of IBD are weakened after diabetic hyperglycemia likely due to worsen NE uptake-1 pathway. Thus, targeting sympathetic NE uptake-1 signaling molecules has clinical implications for treatment and management of CHF in diabetes. Our data were also to shed light on strategies for application of this drug because NE and BNP play an important role in regulation of progression and prognosis of CHF, and in particular, because IBD affects NE uptake-1 pathway in hyperglycemic animals to a less degree.

Identification of long non-coding RNAs biomarkers for early diagnosis of myocardial infarction from the dysregulated coding-non-coding co-expression network.

Long non-coding RNAs (lncRNAs) have recently been shown as novel promising diagnostic or prognostic biomarkers for various cancers. However, lncRNA expression patterns and their predictive value in early diagnosis of myocardial infarction (MI) have not been systematically investigated. In our study, we performed a comprehensive analysis of lncRNA expression profiles in MI and found altered lncRNA expression pattern in MI compared to healthy samples. We then constructed a lncRNA-mRNA dysregulation network (DLMCEN) by integrating aberrant lncRNAs, mRNAs and their co-dysregulation relationships, and found that some of mRNAs were previously reported to be involved in cardiovascular disease, suggesting the functional roles of dysregulated lncRNAs in the pathogenesis of MI. Therefore, using support vector machine (SVM) and leave one out cross-validation (LOOCV), we developed a 9-lncRNA signature (termed 9LncSigAMI) from the discovery cohort which could distinguish MI patients from healthy samples with accuracy of 95.96%, sensitivity of 93.88% and specificity of 98%, and validated its predictive power in early diagnosis of MI in another completely independent cohort. Functional analysis demonstrated that these nine lncRNA biomarkers in the 9LncSigAMI may be involved in myocardial innate immune and inflammatory response, and their deregulation may lead to the dysfunction of the inflammatory and immune system contributing to MI recurrence. With prospective validation, the 9LncSigAMI identified by our work will provide additional diagnostic information beyond other known clinical parameters, and increase the understanding of the molecular mechanism underlying the pathogenesis of MI.

Comparison of the efficacy of recombinant human brain natriuretic peptide with saline hydration in preventing contrast-induced nephropathy in patients undergoing coronary angiography with or without concomitant percutaneous coronary intervention.

The incidence of contrast-induced nephropathy has an increasing trend as a result of increased use of contrast media during coronary interventional procedures. Contrast-induced nephropathy is one of the major causes for hospital acquired renal failure after coronary interventional procedures. In this study, a total of 126 enrolled patients undergoing elective coronary angiography and/or percutaneous coronary intervention were randomly divided into two groups to investigate the efficacy of recombinant human brain natriuretic peptide in preventing contrast-induced nephropathy in patients undergoing elective coronary angiography and/or percutaneous coronary intervention. Our results showed that there was no statistically significant difference in the primary end points, with similar incidence of contrast-induced nephropathy in the two groups (P=0.770). In compared with the hydration group, the elevation of serum creatinine in the recombinant human brain natriuretic peptide group was less, especially at 48 hours (P=0.047) and at 72 hours (P=0.048) after the procedure. The creatinine clearance from baseline to 72 hours after the procedure was higher in the BNP group than in the hydration group. There were significant differences in creatinine clearance at 48 hours (P=0.016) and at 72 hours (P=0.019) between the two groups. In spite of similar incidence of contrast-induced nephropathy, recombinant human brain natriuretic peptide has its advantages for the protection of the renal function associated with better protection of renal function in patients undergoing elective coronary angiography and/or percutaneous coronary intervention, compared with saline hydration.

Percutaneous coronary intervention delays pacemaker implantation in coronary artery disease patients with established bradyarrhythmias.

BACKGROUND: Pacemakers have long been used to assist the heart under pathological conditions, and they are the first choice in the treatment of systematic bradyarrhythmias. However, the effect of percutaneous coronary intervention (PCI) in patients with coronary artery disease as well as bradyarrhythmias remains unknown. METHODS: In the present study, 42 patients with chest pain and/or abnormal stress test results were surveyed. Before coronary angiography, patients underwent complete examination, including a 24 h dynamic electrocardiogram, which was used to diagnose bradyarrhythmias that were not suitable for pacemaker implantation due to a lack of arrhythmia-related symptoms. All patients underwent PCI but did not undergo pacemaker implantation. Forty-one patients with chest pain and/or abnormal stress test results, as well as symptom-free bradyarrhythmias, were selected as the control group. All of the patients in the control group were committed to treatments without PCI. RESULTS: During a mean (±SD) of 3.3±0.5 years of follow-up (range 2.5 to 4.5 years), 24 of 42 patients who received PCI underwent pacemaker implantation for arrhythmia-related symptoms, eight were shown by Holter monitoring to have worsened but still exhibited no symptoms, and the remainder did not show any changes according to the examinations performed. In the control group, 31 patients underwent pacemaker implantation for arrhythmia-related symptoms, eight were shown by Holter monitoring to have worsened but still exhibited no symptoms, and two did not show any changes according to the examinations performed. Nevertheless, the rates of pacemaker implantation each year (from the first to the third year) between the two groups were 7.1% versus 39.0% (P=0.001); 33.3% versus 63.4% (P=0.006); and 57.1% versus 75.6%, (P=0.075), respectively. CONCLUSIONS: The present study found that PCI delayed the demand for pacemaker implantation among coronary artery disease patients.

C1 domain mediates CalDAGIII localization to the Golgi.

CalDAGs are a family of Ras guanyl exchange factors that contain calcium and DAG-binding domains. Among the four identified members of CalDAG family, CalDAGIII has been shown to play important role in B lymphocyte and endocrine cell functions. However, the mechanism underlining these functions remain to be determined. Here in the present study, we determined the subcellular localization of CalDAGIII and roles of calcium-binding and DAG-binding domains in its localization. We found that C1 domain but not EF hands is important for both CalDAGIII localization to the Golgi and p38 activation in B cells, indicating that CalDAGIII may be regulated by DAG but not calcium.

[Efficacy comparison with low and high dose nadroparin for patients with acute coronary syndrome underwent percutaneous coronary intervention].

OBJECTIVE: To evaluate the safety and optimal prior percutaneous coronary intervention (PCI) nadroparin dose in patients with acute coronary syndrome (ACS). METHODS: A total of 236 ACS patients were randomly treated with subcutaneously nadroparin 0.075 ml/10 kg (group I, n = 120) and 0.1 ml/10 kg (group II, n = 116) respectively (bid for 48 hours). PCI was the performed 1 h after final nadroparin injection. No additional nadroparin was applied during PCI. Plasmic anti-Xa level was assayed before and at 1, 2, 4 and 8 hours after final nadroparin administration. Adverse clinical events (death, myocardial infarction, need for revascularization) and bleeding events were recorded up to 30 days post PCI. RESULTS: Baseline clinical characteristics as well as the MACE and severe bleeding events between the two groups were similar (all P > 0.05). Plasmic anti-Xa level of group II was significantly higher than that of group I post nadroparin application (P < 0.01). CONCLUSION: Anticoagulation effects and MACE as well as severe bleeding events up to 30 days post PCI were similar with either 0.075 ml/10 kg or 0.1 ml/10 kg nadroparin dose in ACS patients.