Growth differentiation factor 15, ischemia modified albumin and pregnancy-associated plasma protein A in patients with coronary artery disease.

BACKGROUND: Growth differentiation factor 15 (GDF-15), ischemia modified albumin (IMA) might aid in the early diagnosis and risk stratification of patients with coronary artery disease (CAD), while pregnancy associated plasma protein-A (PAPP-A) can serve as a useful marker of vulnerable plaques and acute coronary syndrome (ACS). We sought to determine serum levels of GDF-15, IMA, PAPP-A and evaluate their diagnostic value in different types of CAD. METHODS: We detected serum levels of GDF-15, IMA and PAPP-A in 348 patients with CAD and 205 controls. Levels of high-sensitivity C reactive protein, creatine kinase isoenzyme MB, and high-sensitivity cardiac troponin-T, which represent biomarkers of inflammation, damage or necrosis, were also evaluated. RESULTS: There were significant differences of GDF-15, IMA and PAPP-A in patients with CAD compared with the controls, where GDF-15 seemed to be associated with severity of CAD. GDF-15 demonstrated a sensitivity of 84.0% and specificity of 84.8% for diagnosis of UAP, while the negative predictive value was 87.4%. The sensitivity and specificity, negative predictive value of IMA in the diagnosis of UAP were 70.0%, 69.5%, and 70.0%, respectively. PAPP-A had the lowest sensitivity and negative predictive value compared with other markers. CONCLUSIONS: GDF-15 demonstrated a significant improvement in earlier prediction and assessment of overall patient risk of UAP comparing to IMA and PAPP-A.

Age-specific 99th percentile cutoff of high-sensitivity cardiac troponin T for early prediction of non-ST-segment elevation myocardial infarction (NSTEMI) in middle-aged patients.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) assay is used in the diagnosis and risk assessment of patients with symptoms of myocardial infarction. This study was undertaken to establish an age-specific 99th percentile cutoff value for hs-cTnT in Chinese population, and to evaluate its potential for early prediction of non-ST-segment elevation myocardial infarction (NSTEMI) in middle-aged patients. METHODS: Troponin T levels in blood obtained from healthy Chinese adults were assayed using hs-cTnT. The distribution was plotted and 99th percentiles were determined by nonparametric statistics. Prediction performance at the conventional cutoff (14 ng/L) recommended by the Roche company was compared with the age-specific cutoff for NSTEMI in 100 middle-aged patients (40-60 years of age) with acute chest pain. RESULTS: The 99th percentile for hs-cTnT was 14 ng/L for patients ≥60 years of age and 11 ng/L for those <60. Fifty of the 100 patients were finally diagnosed with NSTEMI. The age-specific 99th percentile cutoff value of 11 ng/L identified a higher number of patients with NSTEMI than the conventional 14 ng/L cutoff (46 vs. 40 patients), although the difference was not statistically significant (P = 0.084). In addition, the sensitivity of hs-cTnT increased from 80 to 92% and the negative predictive values increased from 82.4 to 91.8%. CONCLUSION: Using 11 ng/L as a decision-making cutoff point for hs-cTnT facilitated earlier prediction of NSTEMI in middle-aged patients than the conventional 14 ng/L cutoff. Further studies are needed to confirm this finding in larger group of patients.

MiR-301a promotes embryonic stem cell differentiation to cardiomyocytes.

BACKGROUND: Cardiovascular disease is the leading cause of death worldwide. Tissue repair after pathological injury in the heart remains a major challenge due to the limited regenerative ability of cardiomyocytes in adults. Stem cell-derived cardiomyocytes provide a promising source for the cell transplantation-based treatment of injured hearts. AIM: To explore the function and mechanisms of miR-301a in regulating cardiomyocyte differentiation of mouse embryonic stem (mES) cells, and provide experimental evidence for applying miR-301a to the cardiomyocyte differentiation induction from stem cells. METHODS: mES cells with or without overexpression of miR-301a were applied for all functional assays. The hanging drop technique was applied to form embryoid bodies from mES cells. Cardiac markers including GATA-4, TBX5, MEF2C, and α-actinin were used to determine cardiomyocyte differentiation from mES cells. RESULTS: High expression of miR-301a was detected in the heart from late embryonic to neonatal mice. Overexpression of miR-301a in mES cells significantly induced the expression of cardiac transcription factors, thereby promoting cardiomyocyte differentiation and beating cardiomyocyte clone formation. PTEN is a target gene of miR-301a in cardiomyocytes. PTEN-regulated PI3K-AKT-mTOR-Stat3 signaling showed involvement in regulating miR-301a-promoted cardiomyocyte differentiation from mES cells. CONCLUSION: MiR-301a is capable of promoting embryonic stem cell differentiation to cardiomyocytes.