Effects of selenoprotein S on oxidative injury in human endothelial cells.

BACKGROUND: Selenoprotein S (SelS) is an important endoplasmic reticulum and plasma membrane-located selenoprotein implicated in inflammatory responses and insulin resistance. However, the effects of SelS on endothelial cells (ECs) have not been reported. In the present study, the role of SelS in oxidative stress and the underlying mechanism were investigated in human ECs. METHODS: A SelS over-expression plasmid (pc-SelS) and a SelS-siRNA plasmid were transfected into human umbilical vein endothelial cells (American Type Culture Collection, USA). The cells were divided into four groups: control, SelS over-expression (transfected with pc-SelS), vector control, and SelS knockdown (transfected with siRNA-SelS). After treating the cells with H2O2, the effects of oxidative stress and the expression of caveolin-1 (Cav-1) and protein kinase Cα (PKCα) were investigated. RESULTS: Following treatment with H2O2, over-expression of SelS significantly increased cell viability and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) production and Cav-1 gene and protein expression. However, no effects on PKCα were observed. In contrast, knockdown of SelS significantly decreased cell viability, SOD activity, and PKCα gene and protein expression, and increased MDA production and Cav-1 gene and protein expression. CONCLUSIONS: SelS protects ECs from oxidative stress by inhibiting the expression of Cav-1 and PKCα.

Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS: In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China (RWE-PCSK study).

BACKGROUND: The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE. RESULTS: In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group ( P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE (hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250). CONCLUSIONS: In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

Percutaneous Coronary Intervention in Elderly Patients with Coronary Chronic Total Occlusions: Current Evidence and Future Perspectives.

The proportion of the elderly in the total population of the world is growing, and the number of elderly patients with coronary chronic total occlusions (CTO) is huge. The elderly patients often have more extensive coronary artery disease, more severe ischemic burden and higher risk of cardiovascular events, as compared to younger patients, and thereby they might greatly benefit from coronary revascularization, even though they may have higher risk of operative complications. Most interventional cardiologists are more likely to be reluctant to operate complex percutaneous coronary intervention (PCI) in elderly patients. The latest refinements in dedicated CTO-PCI equipment and techniques have led to high rates of success and low complications rates and have made the CTO-PCI procedures safe and effective among the elderly patients. However, up to now, there is no widely recognized consensus or guideline on treatment strategy of elderly CTO patients, and the prognosis in this population is unknown. In this review, we aim to provide an overview of the current evidence and future perspectives on PCI in elderly patients with CTOs.

[Intracoronary and hypodermic injection of granulocyte colony-stimulating factor improved cardiac function in Swine with chronic myocardial ischemia].

OBJECTIVES: To compare the efficacy and feasibility between intracoronary and hypodermic injection of granulocyte colony-stimulating factor (G-CSF) on improving cardiac function in a Swine model of chronic myocardial ischemia. METHODS: Eighteen Swine underwent placement of ameroid constrictor on left circumflex coronary artery. The presence of myocardial ischemia was verified at four weeks after the operation, and the animals were then randomly assigned into three groups (n = 6 each): (1) administration of vehicle (control), (2) hypodermic injection of G-CSF (5 microgxkg(-1)x;d(-1)) for five days (IH), and (3) intracoronary injection of a bonus G-CSF (60 microg/kg) (IC). Coronary angiogram, cardiac MRI, and (18)F-FDG-SPECT/(99m)Tc-SPECT (DISA-SPECT) measurements were performed at pre-administration and at 4 weeks post administration. Global heart function such as left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVSDV) and left ventricular ejection fraction (LVEF), myocardial perfusion, myocardial viability and myocardial infarct area were evaluated. Myocardial vWF, Bcl-2 and Bax expressions were detected by Western blot and RT-PCR. RESULTS: MRI data showed that left ventricular dilation and dysfunction were similarly prevented in IH and IC G-CSF treated animals at eight weeks after the operation. SPECT revealed that both IH and IC G-CSF equally improved the regional contractility of chronic myocardial ischemia and increased myocardial viability. Myocardial infarct size was also reduced after both G-CSF treatments as detected by MRI. Intracoronary injection of G-CSF did not lead to angiogenesis in other organs. G-CSF treatments were also associated with a significant reduction in myocardial apoptosis and significant increase in angiogenesis. CONCLUSIONS: Both intracoronary and hypodermic injection of G-CSF were safe and feasible and could equally improve cardiac function and increase angiogenesis in this Swine model of chronic myocardial ischemia.

Differences in the cargos and functions of exosomes derived from six cardiac cell types: a systematic review.

Exosomes are bilayer membrane vesicles with cargos that contain a variety of surface proteins, markers, lipids, nucleic acids, and noncoding RNAs. Exosomes from different cardiac cells participate in the processes of cell migration, proliferation, apoptosis, hypertrophy, and regeneration, as well as angiogenesis and enhanced cardiac function, which accelerate cardiac repair. In this article, we mainly focused on the exosomes from six main types of cardiac cells, i.e., fibroblasts, cardiomyocytes, endothelial cells, cardiac progenitor cells, adipocytes, and cardiac telocytes. This may be the first article to describe the commonalities and differences in regard to the function and underlying mechanisms of exosomes among six cardiac cell types in cardiovascular disease.

Preferences and attitudes of young Chinese clinicians about using a shared decision making tools for communicating cardiovascular risk.

OBJECTIVE: This study assesses the attitudes and preferences of Chinese clinicians toward their involvement in shared decision making (SDM). METHODS: From May 2014 to May 2015, 200 Chinese clinicians from two hospitals were enrolled to complete a survey on their attitude towards SDM. We conducted the survey via face-to-face interviews before and after an educational intervention on SDM among young Chinese clinicians. The clinicians were asked to give the extent of agreement to SDM. They also gave the extent of difficulty in using decision aids (DAs) during the SDM process. The variation in the range of responses to each question before and after the SDM intervention was recorded. The frequency of changed responses was analyzed by using JMP 6.0 software. Data were statistically analyzed using Chi-square and Mann-Whitney U tests, as appropriate to the data type. Multiple logistic regressions were used to test for those factors significantly and independently associated with preference for an approach for each scenario. RESULTS: Of the 200 young Chinese clinicians sampled, 59.0% indicated a preference for SDM and a desire to participate in SDM before receiving education or seeing the DA, and this number increased to 69.0% after seeing the DA with the sample video of the SDM process on Statin Choice. However, 28.5% of the respondents still reported that, in their current practice, they make clinical decisions on behalf of their patients. The clinicians who denied a desire to use the DA stated that the main barriers to implement SDM or DA use in China are lack of time and knowledge of SDM. CONCLUSIONS: Most young Chinese clinicians want to participate in SDM. However, they state the main barriers to perform SDM are lack of experience and time. The educational intervention about SDM that exposes clinicians to DAs was found to increase their receptivity.

Selectins modify dendritic cells during atherosclerosis.

Dendritic cells (DCs) are professional antigen-presenting cells (APC) that facilitate the development and progression of atherosclerosis. However, DCs also function as novel "switches" between immune activation and immune tolerance and represent a heterogeneous hematopoietic lineage, with cell subsets in different tissues that show a differential morphology, phenotype, and function. Regulatory DCs, depending on their immature state, can be induced by immunosuppressive modulation, which plays an important part in the maintenance of immunologic tolerance via suppression of the immune response. In this review, we describe the current understanding of the generation of regulatory DCs. The novel role of selectins in the modification of DCs in atherosclerosis is also discussed.

Long-term clinical outcomes of optimal medical therapy vs. successful percutaneous coronary intervention for patients with coronary chronic total occlusions.

OBJECTIVES: There are little data on the long-term clinical outcomes of optimal medical therapy (OMT) compared with successful percutaneous coronary intervention (PCI) in patients with chronic total occlusions (CTOs). METHODS: A total of 388 patients with ≥1 CTO were enrolled from January 2008 to December 2010. 62 patients were excluded, and 326 patients were divided into an OMT group (n = 125) and PCI group (n = 201) according to the initial treatment strategy. Propensity-score matching was also done to adjust for baseline characteristics. The primary outcome was major adverse cardiac event (MACE), included cardiac death, recurrent myocardial infarction, and repeated revascularization. RESULTS: After a mean follow-up of 47.2 ± 20.0 months, there was no significant difference between the two groups with respect to the prevalence of MACE (successful PCI vs. OMT: 29.6% vs. 21.9%, unadjusted hazard ratio [HR] 1.47, 95% confidence interval [CI] 0.95-2.28, p=0.085). After multivariate analyses, there were significant differences in the prevalence of MACE (adjusted HR 1.76, 95% CI 1.09-2.28, p=0.02) and repeated revascularization (2.14; 1.18-3.90, 0.01). In the propensity score-matched population (80 pairs), there were no significant differences in the prevalence of MACE (adjusted HR 1.89, 95% CI 0.96-3.71, p=0.06) and cardiac death (1.30, 0.44-3.80, 0.63) between groups. CONCLUSION: In the treatment of patients with CTOs, successful PCI did not reduce the long-term risk of MACE compared with OMT.

[In vivo cardiac magnetic resonance imaging of superparamagnetic iron oxides-labeled mesenchymal stem cells in swines].

OBJECTIVE: To explore the feasibility of magnetic resonance imaging (MR) on detecting transplanted nanometer small superparamagnetic iron oxides (SPIO) labeled mesenchymal stem cells (MSCs) in swine model with acute myocardial infarction (MI). METHODS: MSCs isolated from swine were incubated with nanometer SPIO for 24 hours and the third-passage MSCs were labeled with DNA dye 4'-6-diamidino-2-phenylindole (DAPI) and aliphatic red fluorescent dye PKH(26)-GL. Presence of small particles of SPIO in MSCs was assessed by Prussian Blue staining and electron microscopy. Three animals in each group received SPIO-labeled MSCs (5 x 10(5); 1 x 10(6); 2 x 10(6)) and MSCs without SPIO (1 x 10(6)) injections into the infarcted myocardium approximately 1 hour following left anterior descending coronary artery. MRI (1.5-T) was performed 20 to 24 hours post infarction in all animals and the animals were subsequently sacrificed for histology 1 hour post MRI. RESULTS: In vitro Prussian Blue staining and electron microscopy examination revealed numerous iron particles in the cytoplasm of MSCs. Low signal intensity spots with the scanning T(2)(*)WI-Flash 2d sequence were detected in all SPIO-MSCs but not in SPIO-negative-MSCs injected myocardial sites in vivo with the clinical 1.5 T scanner. Prussian blue, DAPI and PKH(26) positive cells were detected histologically in sections corresponding to low signal intensity spots area shown on MRI. CONCLUSION: Magnetically labeled MSCs transplanted in myocardial ischemia area of swine can be visualized in vivo with a clinical 1.5-T MRI and could be used for tracking SPIO-MSCs clinically.

[Hyperinsulinemia induced immune maturation of human monocyte derived dendritic cells: bridging between diabetes and atherosclerosis].

OBJECTIVE: Dendritic cells an hyperinsulinemia are both implicated in the pathogenesis of atherosclerosis. The aim of this study is to explore the effect of high concentration of insulin on the maturation of monocyte-derived dendritic cells (MoDCs) and related signal transduction pathways. METHODS: Human monocytes were purified (over 98%) using Anti-CD14 micro-beads and cultured for 5 days with DC Cellgro medium containing rhGM-CSF (100 microg/L) and rhIL-4 (20 microg/L). Immature DC were then incubated with insulin of various concentrations (0, 1, 10, 100 nmol/L) for 24 hours in the presence or absence of LY294002 (PI3K inhibitor) or PD98059 (MAPK inhibitor). Immunophenotypic expression of CD86 and CD83 were detected using flow cytometry. Endocytosis function of the MoDCs was evaluated using FITC-Dextran and MoDCs secretion IL-12, IFN-gamma and TNF-alpha were measured by ELISA. RESULTS: Insulin induced significantly higher CD83 and CD86 expressions on MoDCs in a dose-dependent manner. The endocytosis function of MoDCs were significantly inhibited and cytokine secretions of IL-12, IFN-gamma and TNF-alpha significantly increased by 10 nmol/L and 100 nmol/L insulin. These effects could be blocked by the LY294002 and PD98059. CONCLUSION: Hyperinsulinemia contributed to atherosclerosis via stimulating immune maturation of MoDCs via both PI3K and MAPK pathways.

[Evaluation of myocardial viability with 201Tl/18F-FDG DISA-SPECT technique in patients with acute myocardial infarction after emergent intracoronary autologous bone marrow mononuclear cells transplantation].

OBJECTIVE: To evaluate the myocardial viability with (201)Tl/(18)F-FDG DISA-SPECT technique in patients with acute myocardial infarction underwent emergent intracoronary autologous bone marrow mononuclear cells (BM-MNC) transplantation. METHODS: Patients with first acute myocardial infarction underwent emergent percutaneous coronary intervention (PCI) were randomized in a 1:1 ratio to either intracoronary transplantation of autologous BM-MNC (n = 20) or to sodium chloride concluding heparin (control, n = 20) via a micro infusion catheter group immediately after PCI. Change in global left ventricular function (LVEF measured by echocardiography) and the myocardial viability detected by (201)Tl/(18)F-FDG DISA-SPECT from baseline and 6-months post transplantation were analyzed. RESULTS: Left ventricular ejection fraction (LVEF) was improved in both groups and the absolute increase (DeltaLVEF) in BM-MNC group was significantly higher than that in control group (7.6% +/- 2.8% vs. 3.0% +/- 2.8%, P < 0.001). In addition, the absolute decrease of myocardial infusion defect detected by (201)Tl SPECT was more significant in BM-MNC group than that in control group (6.7% +/- 3.0% vs. 2.6% +/- 2.6%, P < 0.001) and the number of mismatched segments (indicating viable myocardium) detected by (18)F-FDG SPECT in border zone was also significantly higher in BM-MNC group than that in control group. CONCLUSION: Improved myocardial viability and reduced myocardial infusion defect post emergent intracoronary transplantation of autologous BM-MNC in patients with acute myocardial infarction could be detected by (201)Tl/(18)F-FDG DISA-SPECT technique.

Effects of timing on intracoronary autologous bone marrow-derived cell transplantation in acute myocardial infarction: a meta-analysis of randomized controlled trials.

BACKGROUND: Several cell-based therapies for adjunctive treatment of acute myocardial infarction have been investigated in multiple clinical trials, but the timing of transplantation remains controversial. We conducted a meta-analysis of randomized controlled trials to investigate the effects of timing on bone marrow-derived cell (BMC) therapy in acute myocardial infarction (AMI). METHODS: A systematic literature search of PubMed, MEDLINE, and Cochrane Evidence-Based Medicine databases from January 2000 to June 2017 was performed on randomized controlled trials with at least a 3-month follow-up for patients with AMI undergoing emergency percutaneous coronary intervention (PCI) and receiving intracoronary BMC transfer thereafter. The defined end points were left ventricular (LV) ejection fraction, LV end-diastolic and end-systolic index. The data were analyzed to evaluate the effects of timing on BMC therapy. RESULTS: Thirty-four RCTs comprising a total of 2,307 patients were included; the results show that, compared to the control group, AMI patients who received BMC transplantation showed significantly improved cardiac function. BMC transplantation 3-7 days after PCI (+3.32%; 95% CI, 1.91 to 4.74; P < 0.00001) resulted in a significant increase of left ventricular ejection fraction (LVEF). As for the inhibitory effect on ventricular remodeling, BMC transplantation 3-7 days after PCI reduced LV end-diastolic indexes (-4.48; 95% CI, -7.98 to -0.98; P = 0.01) and LV end-systolic indexes (-6.73; 95% CI, -11.27 to -2.19; P = 0.004). However, in the groups who received BMC transplantation either within 24 hours or later than 7 days there was no significant effect on treatment outcome. In subgroup analysis, the group with LVEF ≤ 50% underwent a significant decrease in LV end-diastolic index after BMC transplantation (WMD = -3.29, 95% CI, -4.49 to -2.09; P < 0.00001); the decrease was even more remarkable in the LV end-systolic index after BMC transplantation in the group with LVEF ≤ 50% (WMD = -5.25, 95% CI, -9.30 to -1.20; P = 0.01), as well as in patients who received a dose of 10^7-10^8 cells (WMD = -12.99, 95% CI, -19.07 to -6.91; P < 0.0001). In the group with a follow-up of more than 12 months, this beneficial effect was significant and increased to a more pronounced effect of +3.58% (95% CI, 1.55 to 5.61; P = 0.0006) when compared with control. CONCLUSIONS: In this meta-analysis, BMC transfer at 3 to 7 days post-AMI was superior to transfer within 24 hours or more than 7 days after AMI in improving LVEF and decreasing LV end-systolic dimensions or LV end-diastolic dimensions. It is more effective in patients with lower baseline LVEF (≤50%) and the effect can last more than 12 months.

[Long term follow-up on emergent intracoronary autologous bone marrow mononuclear cell transplantation for acute inferior-wall myocardial infarction].

OBJECTIVE: To investigate the effects of emergent intracoronary autologous bone marrow mononuclear cell (BM-MNC) transplantation on left ventricular function and myocardium lesion area in patients with first acute inferior-wall myocardial infarction. METHODS: Forty patients with first onset of acute inferior-wall myocardial infarction, 28 males and 12 females, aged < or = 75, treated with emergent percutaneous coronary intervention (PCI) were randomly divided into 2 equal groups: group undergoing intracoronary transplantation of autologous BM-MNC via a micro-catheter right after PCI (BM-MNC group), and control group receiving normal saline and heparin. Blood routine examination, myocardium zymogram, and serum high sensitive C reactive protein (hsCRP) were detected, and 24-hour dynamic electrocardiography, delayed-enhancement myocardial magnetic resonance imaging (CMR), and angiography of the coronary artery and left ventricle were conducted before the transplantation and immediately, 1 week, and 6 months after transplantation. RESULTS: CMR showed that 6 months later the left ventricular ejection fraction (LVEF) of the control group was 47.9% +/- 6.7%, significantly higher than that 1 week later (43.4% +/- 6.7%, P = 0.001), and the LVEF of the BM-MNC group 6 months later was 51.5% +/- 5.2%, significantly higher than that 1 week later (44.5% +/- 7.1%, P = 0.001; however, the absolute change of LVEF (DeltaLVEF) of the BM-MNC group was 6.95% +/- 3.33%, significantly higher than that of the control group (4.05% +/- 1.68%, P = 0.047). Six months later the myocardial lesion area of the BM-MNC group decreased more significantly in comparison with the control group. Nevertheless, there was no difference in change of left ventricular end diastolic volume (LVEDV) between these two groups. The serum hsCRP 48 h after transplantation of the BM-MNC group was 2.8 g/L +/- 0.8 g/L, significantly lower than that before transplantation (13.4 g/L +/- 3.6 g/L, P < 0.001). No severe clinical events, such death, recurrent cardiac infarction, malignant arrhythmia, occur in these 2 groups. CONCLUSION: Emergent intracoronary transplantation of autologous BM-MNC in patients with acute inferior-wall myocardial infarction improves the left ventricular function and myocardial infusion, minimizes the myocardial lesion area significantly.

[Effects and mechanism of hyperglycemia on development and maturation and immune function of human monocyte derived dendritic cells].

OBJECTIVE: Dendritic cells play an important role in the pathogenesis of atherosclerosis. To explore the effects of hyperglycemia on the maturation and immune function of human monocyte derived dendritic cells (MDCs). METHODS: Immature MDCs were cultured in RPMI1640 medium with either 5.5 mmol/L D-glucose (NG), 25 mmol/L D-glucose (HG) or 5.5 mmol/L D-glucose + 19.5 mmol/L mannitol (HM) in the absence or presence of 30 mmol/L N-acetylcysteine [NAC, a reactive oxygen species inhibitor (ROS)] for 48 hours. FACS was used to investigate the MDCs immunophenotypic expression. Immune function was evaluated by allogeneic mixed T lymphocyte reaction and measurement of cytokine levels from culture supernatants. Intracellular ROS production in MDCs was also measured by 2', 7'-dichlorodihydrofluorescein (DCF, 10 micromol/L) fluorescence using confocal laser-scanning microscopy techniques. RESULTS: Compared with NG and HM treated MDCs, the expression of maturation markers such as CD1a, HLA-DR, CD83, CD86 were significantly upregulated, allogeneic T cells proliferation as well as the cytokines secretions (IL-2, IL-12, IL-10 and IFN-gamma) significantly increased in HG treated MDCs. Intracellular ROS production in MDCs was also significantly increased and all these stimulatory effects of HG could be partially attenuated by NAC. CONCLUSION: High glucose promote the maturation of MDCs and augment their capacity to stimulate T-cell proliferation and cytokine secretions at least in part through enhancing intracellular ROS generation. These stimulating effects of high glucose on MDCs maturation may be one of the mechanisms of accelerated atherosclerosis found in patients with diabetes.

[Observation on the safety: clinical trail on intracoronary autologous bone marrow mononuclear cells transplantation for acute myocardial infarction].

OBJECTIVE: To investigate the safety of autologous bone marrow mononuclear cell (BM-MNCs) transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI). METHODS: One hundred and eighty-four patients with AMI treated with percutaneous coronary intervention (PCI) were randomized in a 1:1 way to either intracoronary transplantation of autologous BM-MNCs (n = 92) right after PCI or to sodium chloride concluding heparin (controlled, n = 92) via a micro infusion catheter. In the process of the intracoronary infusion of BM-MNCs, the complications should be recorded, which were aberration reflect (including of pale, syncope, nausea, hypotension and shock), deterioration of angina or heart failure, arrhythmias (including of bradycardia, sinus arrest or atrial ventricular block or ventricular fibrillation), embolism etc. Body temperature, blood pressure and heart rates should be monitored during the first week after transplantation. Holter, coronary angiography and ultrasonic cardiography were performed at the designed time points. Main heart accidents, restenosis and tumor were recorded during 2-years follow up. RESULTS: During the period of bone marrow puncture and intracoronary infusion of BM-MNCs, few patients occurred pale, dizziness, bradycardia and hypotension, which were transient and due to vagus reflect. No stem cell-related arrhythmias, deterioration of angina were noted. In BM-MNCs group one patient developed in-stent reocclusion in one week after transplantation, five developed in-stent restenosis during further follow-up 30 months, which were similar with control group. There were no deaths, major adverse cardiac events, tumor and other late adverse events during follow-up period in both groups. CONCLUSION: Intracoronary transplantation of autologous BM-MNCs in the acute phase after AMI is feasible and seems safe in the 30 months of follow-up.

[Transplantation of autologous bone marrow mononuclear cells on patients with idiopathic dilated cardiomyopathy: early results on effect and security].

OBJECTIVE: The aim of this study is to identify short-term result of cell transplantation in idiopathic dilated cardiomyopathy (IDC) patients who were treated by intracoronary transplantation of autologous mononuclear bone marrow cells (BMCs) in addition to standard therapy. METHODS: Based on given standard therapy, eighteen patients with idiopathic dilated cardiomyopathy were enrolled and divided into transplantation group and control group. The clinical characteristics of two groups were comparable. Among these patients, 10 patients were performed percutaneous coronary autologous BMCs transplantation. Blood routine test, hepatic function, renal function, glucose, triglyceride (TG), cholesterol, low density cholesterol (LDL), high density cholesterol (HDL), uric acid (UA) and high sensitive C-reactive protein (hsCRP) were measured at the time point of pre-operation and some time after transplantation. All patients were monitored under ultrasonic cardiography, Holter, six-minute-walk test and magnetic resonance imaging over a period of at least 6 months. Annual hospital days were recorded during two-year follow-up. RESULTS: Blood routine test, hepatic function, renal function, glucose, TG, cholesterol, LDL, HDL, UA and hsCRP had no significant differences among 48 hours, 3 months and 6 months after transplantation compared with control and pre-transplantation (P > 0.05). Six-minute-walk distance elevated significantly six months after BMCs transplantation compared with control and pre-transplantation [(494.3 +/- 62.8) m vs (307.2 +/- 75.0) m, (321.5 +/- 63.7) m, P < 0.05]. Left ventricular ejection fraction (LVEF) and the sizes of LVEDd had no significant changes compared with that of control and pre-transplantation (P > 0.05). Myocardium lesion area measured by (MRI) seemed decrease in transplantation group compared with that of control and pre-operation [(4.96 +/- 0.47) cm(2) vs (5.12 +/- 0.54) cm(2), (5.02 +/- 0.39) cm(2), P > 0.05], but there was no significance. None of proarrhythmias and side effects had been observed around transplantation and 2 years follow-up. There was no significant difference in survival between two groups in 2 years follow-up. Interestingly, annual hospital day in BMCs transplantation patients was significantly shorter than that in control group [(30.2 +/- 11.2) d vs (43.6 +/- 9.8) d, P < 0.05]. CONCLUSIONS: Autologous bone marrow mononuclear cells transplantation can prolong six-minute-walk, decrease re-hospitalization rate, elevate exercise ability and help to improve cardiac function in patients with IDC. In addition, it was demonstrated that cell transplantation is safe.

Stem cell transplantation dose in patients with acute myocardial infarction: A meta-analysis.

OBJECTIVE: To evaluate whether stem cell transplantation improves global left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction (AMI), and to determine the appropriate stem cell therapy dose as well as the effective period after stem cell transplantation for therapy. METHODS: A systematic literature search included Pubmed, MEDLINE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Cochrane Evidence-Based Medicine databases. The retrieval time limit ranged from January 1990 to June 2016. We also obtained full texts through manual retrieval, interlibrary loan and document delivery service, or by contacting the authors directly. According to our inclusion and exclusion criteria, data were extracted independently by two evaluators. In case of disagreement, a joint discussion occurred and a third researcher was utilized. Data were analyzed quantitatively using Revman 5.2. Summary results are presented as the weighted mean difference (WMD) with 95% confidence intervals (CIs). We collected individual trial data and conducted a meta-analysis to compare changes in global left ventricular ejection fraction (ΔLVEF) after stem cell therapy. In this study, four subgroups were based on stem cell dose (≤1 × 107 cells, ≤1 × 108 cells, ≤1 × 109 cells, and ≤1 × 1010 cells) and three subgroups were based on follow-up time (<6 months, 6-12 months, and ≥12 months). RESULTS: Thirty-four studies, which included 40 randomized controlled trials, were included in this meta-analysis, and 1927 patients were evaluated. Changes in global LVEF were significantly higher in the stem cell transplantation group than in the control group (95% CI: 2.35-4.26%, P < 0.01). We found no significant differences in ΔLVEF between the bone marrow stem cells (BMCs) group and control group when the dose of BMCs was ≤1 × 107 [ΔLVEF 95% CI: 0.12-3.96%, P = 0.04]. The ΔLVEF in the BMCs groups was significantly higher than in the control groups when the dose of BMCs was ≤1 × 108 [ΔLVEF 95% CI: 0.95-4.25%, P = 0.002] and ≤1 × 109 [ΔLVEF 95% CI: 2.31-4.20%, P < 0.01]. In addition, when the dose of BMCs was between 109 and 1010 cells, we did not observe any significant differences [ΔLVEF 95% CI: -0.99-11.82%, P = 0.10]. Our data suggest stem cell therapy improves cardiac function in AMI patients when treated with an appropriate dose of BMCs. CONCLUSION: Stem cell transplantation after AMI could improve global LVEF. Stem cells may be effectively administered to patients with AMI doses between 108 and 109 cells.

[Stem cells transplantation for ischemic heart disease].

At present, no effective therapeutic option for ischemic heart disease is available. The majority of the data on stem cell transplantation coming from preclinical animal studies and clinical research in small scale demonstrate that it may improve cardiac function. However, serious questions about its safety have yet to be answered.