Enhanced differentiation potential of human amniotic mesenchymal stromal cells by using three-dimensional culturing.

The therapeutic potential of human amniotic mesenchymal stromal cells (hAMSCs) remains limited because of their differentiation towards mesenchymal stem cells (MSCs) following adherence. The aim of this study was to develop a three-dimensional (3-D) culture system that would permit hAMSCs to differentiate into cardiomyocyte-like cells. hAMSCs were isolated from human amnions of full-term births collected after Cesarean section. Immunocytochemistry, immunofluorescence and flow cytometry analyses were undertaken to examine hAMSC marker expression for differentiation status after adherence. Membrane currents were determined by patch clamp analysis of hAMSCs grown with or without cardiac lysates. Freshly isolated hAMSCs were positive for human embryonic stem-cell-related markers but their marker profile significantly shifted towards that of MSCs following adherence. hAMSCs cultured in the 3-D culture system in the presence of cardiac lysate expressed cardiomyocyte-specific markers, in contrast to those maintained in standard adherent cultures or those in 3-D cultures without cardiac lysate. hAMSCs cultured in 3-D with cardiac lysate displayed a cardiomyocyte-like phenotype as observed by membrane currents, including a calcium-activated potassium current, a delayed rectifier potassium current and a Ca(2+)-resistant transient outward K(+) current. Thus, although adherence limits the potential of hAMSCs to differentiate into cardiomyocyte-like cells, the 3-D culture of hAMSCs represents a more effective method of their culture for use in regenerative medicine.

Effect of sequential nicorandil on myocardial microcirculation and short-term prognosis in acute myocardial infarction patients undergoing coronary intervention.

BACKGROUND: This study aims to observe the effects of the intracoronary and peripheral venous administration of nicorandil for the postoperative myocardial microcirculation and short-term prognosis of ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI) treatment. METHODS: A total of 140 STEMI patients were divided into three groups according to different patterns of administration: sequential nicorandil group, intracoronary nicorandil group and control group. The main observation indexes included coronary blood flow and myocardial perfusion immediately after PPCI, while the secondary observation indexes included major adverse cardiovascular events (MACE) and left ventricular ejection fraction (LVEF) during the period of hospitalization. RESULTS: After PPCI, the difference in the proportion of patients with thrombolysis in myocardial infarction (TIMI) flow grade 3 among the three groups was statistically significant (P=0.036), where this proportion was higher in the sequential nicorandil group and intracoronary nicorandil group than in the control group (P=0.022 and P=0.047); The difference in corrected TIMI frame count (CTFC) among the three groups was statistically significant (P=0.022), where CTFC was lower in the sequential nicorandil group and intracoronary nicorandil group than in the control group (P=0.010, P=0.031); The differences in the proportion of patients with complete ST resolution (STR) and advancing of enzyme peak time to within 12 h between each two groups were statistically significant (P<0.001), where this proportion was the highest in the sequential nicorandil group; The difference in the CK-MB peak among the three groups was statistically significant (P=0.036), where the CK-MB peak was lower in the sequential nicorandil group than in the control group (P=0.012); The difference in the incidence of MACE between each two groups was statistically significant (P<0.001), where this incidence was the lowest in the sequential nicorandil group; The differences in the proportion of patients with advancing of enzyme peak time to within 14 h and LVEF among the three groups were not statistically significant (P=0.722 and P=0.284). CONCLUSIONS: Compared with intracoronary use alone, the intracoronary and peripheral intravenous use of nicorandil can better improve myocardial microcirculation and short-term prognosis.

Human Plasma Metabolomics Implicates Modified 9-cis-Retinoic Acid in the Phenotype of Left Main Artery Lesions in Acute ST-Segment Elevated Myocardial Infarction.

The detection of left main coronary artery disease (LMCAD) is crucial before ST-segment elevated myocardial infarction (STEMI) or sudden cardiac death. The aim of this study was to identify characteristic metabolite modifications in the LMCAD phenotype, using the metabolomics technique. Metabolic profiles were generated based on ultra-performance liquid chromatography and mass spectrometry, combined with multivariate statistical analysis. Plasma samples were collected prospectively from a propensity-score matched cohort including 44 STEMI patients (22 consecutive LMCAD and 22 non-LMCAD), and 22 healthy controls. A comprehensive metabolomics data analysis was performed with Metaboanalyst 3.0 version. The retinol metabolism pathway was shown to have the strongest discriminative power for the LMCAD phenotype. According to biomarker analysis through receiver-operating characteristic curves, 9-cis-retinoic acid (9cRA) dominated the first page of biomarkers, with area under the curve (AUC) value 0.888. Next highest were a biomarker panel consisting of 9cRA, dehydrophytosphingosine, 1H-Indole-3-carboxaldehyde, and another seven variants of lysophosphatidylcholines, exhibiting the highest AUC (0.933). These novel data propose that the retinol metabolism pathway was the strongest differential pathway for the LMCAD phenotype. 9cRA was the most critical biomarker of LMCAD, and a ten-metabolite plasma biomarker panel, in which 9cRA remained the weightiest, may help develop a potent predictive model for LMCAD in clinic.

[Risk factors for coronary artery disease stimulate urokinase receptor expression on monocytes].

OBJECTIVE: To evaluate the effect of risk factors for coronary artery disease (CAD) on urokinase receptor (uPAR) expression on monocytes. METHODS: A total of 106 patients were enrolled and divided into five risk-factor groups: sixteen with hypertension, twenty-four with dyslipidemia, eighteen with hypertension + obesity, eighteen with dyslipidemia + obesity and thirty with hypertension + dyslipidemia + obesity. Seventeen healthy volunteers were recruited as control group. Monocyte expression of uPAR and mean fluorescence intensity index (MFI Index) of uPAR were measured by flow cytometer (FACSCalibur). RESULTS: No difference in monocyte uPAR expression was detected between hypertension and control group [(4.9 +/- 12.5)% vs. (7.7 +/- 10.3)%, P=0.74]. However, the uPAR expression was raised to (23.7 +/- 22.5)% in hyperlipidemia group, a 3.9- and a 2.1-fold increase compared with those in hypertension (P<0.01) and control group (P<0.05), respectively. When combined with obesity, uPAR expression was elevated further to (32.9 +/- 30.8)% in hypertension + obesity group, (37.4 +/- 31.4)% in dyslipidemia + obesity group and (23.8 +/- 20.5)% in hypertension + dyslipidemia + obesity group, all having statistical significance compared with control group or hypertension group (P<0.01). The results were the same when corrected by age, BMI and hs-CRP. uPAR MFI Index was increased from 0.78 +/- 0.86 in control group to 1.91 +/- 1.97 and 3.33 +/- 2.52 in dyslipidemia group and hypertension + obesity group, respectively, P<0.05. Linear regression analysis revealed a significant correlation between uPAR expression and FBG concentration in dyslipidemia group, r=0.72, P=0.04. CONCLUSIONS: uPAR expression was elevated on monocytes in patients with risk factors for CAD. Dyslipidemia and obesity may contribute to the increase of uPAR expression.

Ischemic Postconditioning Before Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction Reduces Contrast-induced Nephropathy and Improves Long-term Prognosis.

BACKGROUND AND AIMS: Contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) is one of the major adverse outcomes affecting the prognosis of patients with acute ST-segment elevation myocardial infarction (STEMI). Ischemic postconditioning prior to PCI (pre-PCI) in patients with STEMI is hypothesized to be protective against CIN after PCI. METHODS: A total of 251 patients with STEMI were randomized into two groups: ischemic postconditioning group (n = 123, age, 61.1 ± 12.5 years) who underwent ischemic postconditioning prior to PCI; control group (n = 128; age, 64.1 ± 12.1 years) who underwent only PCI. Ischemic postconditioning was administered by three cycles of deflation and inflation of the balloon (1-min ischemia and 1-min reperfusion) starting 1 min after infarct-related artery (IRA) opening. Diagnostic criterion for CIN was: increase in serum creatinine level by ≥0.5 mg/dL or by ≥25% increase from preoperative level within 48 h of surgery. All patients were followed for 1 year for incidence of major cardiovascular events (MACE). RESULTS: The incidence of postoperative CIN in the ischemic postconditioning group was 5.69% as compared to 14.06% in the control group (p <0.05). At one year, the MACE incidence in the ischemic postconditioning group was 7.32% as compared to 15.63% in the control group (p <0.05). CONCLUSIONS: Pre-PCI ischemic postconditioning in STEMI patients significantly reduces the post-PCI incidence of CIN and improves long-term prognosis.