Effect of EPO on PRDM16, FGF21 expression and STAT phosphorylation of brown adipose tissue in HFD mice / 中国应用生理学杂志

OBJECTIVE@#To investigate the effect of erythropoietin (EPO) on blood glucoseand plasma insulin level, index of insulin resistance (HOMA-IR), introperitoneal glucose tolerance test (IPGTT), the mRNA and protein level of PR domain-containing 16 (PRDM16), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), fibroblast growth factor 21 (FGF21) of brown adipose tissue (BAT) in mice fed with high fat diet (HFD) in order to provide clues for the mechanism of obesity and complication.@*METHODS@#Twenty C57BL/6J male mice fed with HFD were randomly divided into control group (HFD-Con) and EPO group (HFD-EPO), mice in the two groups were injected intraperitoneally normal saline and EPO (200 IU/kg) res pectively, 3 times per week for consecutive 4 weeks.Then the body weight, blood glucose, plasma insulin level, HOMA-IR and IPGTT were detected.The mRNA and protein level of PRDM16, FGF21, p-STAT3/STAT3 in brown adipose tissue were detected by real-time quantitative RT-PCR and Western blot respectively.@*RESULTS@#After intraperitoneal injection of EPO for 4 weeks, the body weight of the mice in HFD-EPO and HFD-Con groups was (26.65±0.85) g and (31.50±1.6 0) g respectively.The blood glucose of the mice in HFD-EPO group[(62.79±8.09) mg/dl]was significantly decreased compared with that in HFD-Con group[(91.06±9.86) mg/dl].The plasmainsulin level in HFD-EPO group[(10.56±1.06)μU/ml]was significantly decreased compared with that in HFD-Con group[(13.2±1.1)μU/ml, < 0.01].The level of IPGTT in HFD-EPO group was significantly ameliorated and th e HOMA-IR decreased compared with those in HFD-Con group.The mRNA and protein expressions of PRDM16, FGF21 and the level of STAT3 of brown adipose tissue in HFD-E PO group were increased obviously.And there was no difference of FGF21 mRNA content in liver and FGF21 content in plasmabetween the two groups.@*CONCLUSIONS@#EPO could promote differentiation of brown adipose tissue by increase in the express ion of PRDM16, and decrease the blood glucose level, ameliorate glucose metabolism in obses mice.

Meta-analysis for Vitamins Preventing Contrast Induced Nephropathy in Patients After Coronary Angiography / 中国循环杂志

Objective: To evaluate the effects for vitamins preventing contrast induced nephropathy (CIN) in patients after coronary angiography (CAG) by Meta-analysis. Methods: We searched PubMed, Medline, Cochrane library central register of controlled trials and ClinicalTrails. gov from the database establishment to 2016-12 for CIN related references. According to enrollment and elimination standards, we chose eligible randomize control trail (RCT), extracted data and conducted a Meta-analysis using RevMan 5.3 statistical software. Results: A total of 11 RCTs with 1810 patients were enrolled which included in 2 groups: Vitamins group, n=951 and Placebo group, n=859. The average age of patients was (60-73) years and the male was (45.9-92.2) %. Meta-analysis showed that CIN occurrence rate in Vitamins group was lower than Placebo group (RR=0.54, 95% CI 0.39-0.73); compared with Placebo group, the incidence of CIN was decreased by 46% in Vitamins group. Using Vitamin C could decrease CIN occurrence rate (RR=0.58, 95% CI 0.37-0.90); compared with Placebo group, the incidence of CIN was decreased by 42% for using Vitamin C. Conclusion: Vitamins can reduce 46% incidence of CIN and Vitamin C may reduce 42% incidence of CIN in patients after CAG.

Safety and efficacy of the second generation biodegradable polymer Cobalt-Chromium sirolimus-eluting stent (EXCEL 2) stent in diabetic patients:A Subgroup analysis of the CREDIT Ⅱ and CREDIT Ⅲ trials / 中国介入心脏病学杂志

Objective To invesgate the safety and efficacy of the second generation biodegradable polymer Cobalt-Chromium sirolimus-eluting stent (EXCEL2) stent in diabetic patients by a subgroup analysis of of the CREDITⅡand CREDIT Ⅲ trials. Methods All patients who were implanted with the EXCEL2 stent were enrolled in the CREDITⅡand CREDIT Ⅲ trials. The primary endpoint was target lesion failure at 24-month, defi ned as a composite of cardiac death, target vessel myocardial infarction (TV-MI) and target lesion revascularization(TLR). The secondary endpoint was endpoints including all-cause death, all myocardial infarction (MI) or any revascularization.Results A total of 828 patients were included from the patients who were implanted with the EXCEL2 stent in the CREDIT II and CREDIT Ⅲ trials. 24-month follow-up rate was 99.5%. There was no significant difference in the primary endpoint (P>0.05) and event rates of the secondary endpoints(P>0.05) between the diabetic and non-diabetic group, which included all-cause death[diabetics (2.5%)vs.non-diabetics(1.4%),P>0.05],myocardial infarction(MI)(7.5% vs.5.0%,P>0.05),all from of revascularization(5.0% vs.3.9%,P>0.05),and stent thrombosis(0.6% vs.0.4%,P>0.05).Conclusions EXCEL 2 stent met the objective performance goal on effcacy and safety, which can reduce make stent restenosis, target vessel revascularization ,with 160 diabetic cases among them, and stent thrombosis in diabetic patients.

Impact and related mechanisms of stromal cell-derived factor-1α on serum deprivation-induced cardiac stem cells apoptosis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the impact and related mechanisms of stromal cell-derived factor-1α (SDF-1α) on serum deprivation-induced apoptosis of cardiac stem cells (CSCs).</p><p><b>METHODS</b>CSCs were isolated from adult mouse heart tissue and cultured in vitro. Obtained cells were purified using magnetic-activated cell sorting (MACS) with c-kit magnetic beads. C-kit(+)CSCs were divided into five groups: normal control group, serum deprivation group, serum deprivation+SDF-1α group, serum deprivation+SDF-1α+AMD3100 group, serum deprivation+SDF-1α+LY294002 group. Cell apoptosis was assessed using the DeadEnd Colorimetric TUNEL System and flow cytometry analyses with an Annexin V-FITC Apoptosis Detection Kit. The viability of CSCs was assessed by CCK-8. The protein expression of Bcl-2 and phosphorylated Akt were detected by Western blot. The caspase-3 activity was determined using caspase-3 Colorimetric Assay Kit.</p><p><b>RESULTS</b>After magnetic separation, more than 85% of cardiosphere derived cells were positive for c-kit expression. Compared with the normal control group, the apoptosis rate of serum deprivation group was significantly increased[(27.03 ± 0.80)% vs. (1.51 ± 0.54)%, P < 0.01], which could be significantly reduced by SDF-1α in a concentration dependent manner and peak effect was seen with 100 ng/ml SDF-1α[(10.67 ± 1.06)% vs. (27.03 ± 0.80)%, P < 0.01]. The expressions of p-Akt and Bcl-2 were significantly increased and the activity of caspase-3 was significantly decreased in serum deprivation+SDF-1α group compared to serum deprivation group (P < 0.01). Further more, the expression of p-Akt and Bcl-2 were significantly decreased and the activity of caspase-3 was increased in both serum deprivation+SDF-1α+AMD3100 group and serum deprivation+SDF-1α+LY294002 group compared to serum deprivation+SDF-1α group (P < 0.01).</p><p><b>CONCLUSIONS</b>SDF-1α reduces serum deprivation induced CSCs apoptosis via modulating PI3K/Akt signaling pathway.</p>

Long-term effects of bone marrow-derived cells transplantation in patients with acute myocardial infarction: a meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The long-term effects of bone marrow-derived cells (BMC) transplantation in patients with acute myocardial infarction (AMI) have not been established. The present meta-analysis of randomized controlled trials with follow-up ≥ 2 years was performed to investigate the long-term effects of BMC therapy in patients after AMI.</p><p><b>METHODS</b>Specific terms were used to conduct a systematic literature search of MEDLINE, EMBASE, the Cochrane Library and the Cochrane Central Register of Controlled Trials, and the China Biological Medicine Disk database from their inception to March 2012. A standardized protocol was used to extract information, and random effect model was used to analyze all data except major adverse events.</p><p><b>RESULTS</b>Five trials comprising 510 patients were included. Compared with controls, BMC therapy significantly improved left ventricular ejection fraction (LVEF) (4.18%, 95%CI: 2.02% to 6.35%, P = 0.0002), while mildly but not significantly reduced left ventricular end-systolic volume (-4.47 ml, 95%CI: -10.92 to 1.99, P = 0.17) and left ventricular end-diastolic volume (-2.29 ml, 95%CI: -9.96 to 5.39, P = 0.56). Subgroup analysis revealed that significant improvement of LVEF induced by BMC therapy could be observed in patients with baseline LVEF ≤ 42%, but disappeared in those with baseline LVEF > 42%. There were trends in favor of BMC therapy for most major clinical adverse events, though most differences were not significant.</p><p><b>CONCLUSIONS</b>Intracoronary BMC infusion in patients with AMI seems to be safe and may further improve LVEF on top of standard therapy; especially the beneficial effects could last for long term. The findings need to be validated in the future.</p>

Efficacy of regional renal nerve blockade in patients with chronic refractory heart failure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Increased renal sympathetic nerve activity can result in diuretic resistance in patients with chronic congestive heart failure. We investigated the effect of regional renal nerve blockade on the patients with chronic refractory heart failure and diuretic resistance.</p><p><b>METHODS</b>Eighteen patients with chronic refractory heart failure were enrolled (mean age (64 ± 11) years). The patients were randomly divided into two groups (renal nerve blockade group and standard therapy group, n = 9 each). Renal nerve blockade was performed by percutaneous injection of local anaesthetic under computed tomographic guidance. Heart rate, mean arterial blood pressure, plasma and urine electrolytes, neurohormones, factional excretion of sodium (FENa), 24-hour urine volume were monitored at baseline and the first 24 hours after therapy. Dyspnea and oedema were also evaluated. The major adverse cardiovascular events (MACE), plasma brain natriuretic peptide (BNP) level and left ventricular ejection fraction (LVEF) were compared between the two groups during the 3 - 12 months follow-up period.</p><p><b>RESULTS</b>No complication was observed during the acute phase of renal nerve blockade. After renal nerve blockade, the 24-hour urine volume and FENa were significantly increased, while the level of plasma rennin, angiotensin II, aldosterone, BNP and atrial natriuretic peptide as well as dyspnea and oedema were significantly reduced in renal nerve blockade group compared with baseline and standard therapy group. During three to 12 months of follow-up, the rate of MACE and plasma BNP level were significantly lower, while LVEF was significantly higher in renal nerve blockade group than those in standard therapy group.</p><p><b>CONCLUSION</b>Regional renal nerve blockade may be a safe and effective treatment for patients with chronic refractory heart failure.</p>

Association study on the microRNA-1 target gene polymorphism and the risk of premature coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between the genetic variant of miRNA-1 target gene COG6 rs9548934 C→T and the risk of premature coronary artery disease (pCAD).</p><p><b>METHODS</b>This study included 226 pACD patients and 275 gender and age matched pCAD-free controls hospitalized in our hospital, diagnosis was made based on coronary angiography (CAG) results. The genotypes of miRNA-1 target gene COG6 rs9548934 C→T were detected by PCR-RFLP.</p><p><b>RESULTS</b>Compared with the wide genotype CC, subjects with the variant genotypes CT of rs9548934 C→T was associated with a 45% lower risk of pACD (adjusted OR = 0.55, 95%CI = 0.36 - 0.82, P = 0.003), and the subjects with CT/TT genotypes were also associated with a significantly lower risk of pACD (adjusted OR = 0.64, 95%CI = 0.44 - 0.92, P = 0.015). Using the median serum TG level (1.20 mmol/L) in control group as the cutoff value, subjects with higher serum TG levels were associated with increased risk of pACD after adjustment for age, gender and BMI (adjusted OR = 2.32, 95%CI = 1.57 - 3.41, P < 0.001). In addition, subjects with higher HDL-C levels were associated with significantly lower risk of pACD (adjusted OR = 0.48, 95%CI = 0.31 - 0.75, P = 0.001). Stratified analyses showed that the risk reduction for pCAD in CT/TT genotypes carriers was more significant in the female subjects (adjusted OR = 0.54, 95%CI = 0.30 - 0.97, P = 0.040), and in subjects with lower TG, TC, HDL-C and LDL-C levels (adjusted OR = 0.62, 95%CI = 0.39 - 0.98, P = 0.040; adjusted OR = 0.55, 95%CI = 0.35 - 0.85, P = 0.008; adjusted OR = 0.43, 95%CI = 0.22 - 0.87, P = 0.018; adjusted OR = 0.49, 95%CI = 0.32 - 0.75, P = 0.001, respectively).</p><p><b>CONCLUSION</b>The polymorphism of miRNA-1 target gene COG6 rs9548934C→T is associated with lower risk of pCAD, especially in female subjects and subjects with lower serum lipid levels.</p>

Metalloproteinase Tolloid-like 1 gene mutation in Chinese patients with sporadic congenital heart diseases / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore whether there are gene mutations of Tolloid-like 1 (TLL-1) gene in Chinese patients with sporadic congenital heart disease (CHD).</p><p><b>METHODS</b>One hundred and fifteen patients with sporadic CHD were selected as CHD group. One hundred and two age and gender-matched healthy people were recruited as control group. After amplifying the exon 10 of the TLL-1 gene by polymerase chain reaction, the polymerase chain reaction products were purified, sequenced and analyzed in order to investigate the TLL-1 gene mutation.</p><p><b>RESULTS</b>An insertion mutation of base A in the exon 10 of TLL-1 gene was identified in 7 out of 115 CHD patients, including 3 patients with atrial septal defect, 2 patients with ventricular septal defect, 1 patients with patent ductus arteriosus and 1 patients with complex CHD, the total mutation rate was 6.1% in CHD group and 0 in control group (P < 0.01).</p><p><b>CONCLUSIONS</b>TLL-1 gene mutation with an insertion mutation of base A in exon 10 is often in Chinese patients with various CHD. The underlying pathogenesis between TLL-1 gene mutation and occurrence of congenital heart disease in Chinese people remains unclear and warrants further investigations.</p>

Fatty acid desaturase 1 polymorphisms are associated with coronary heart disease in a Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A recent genome-wide association study in Caucasians revealed that three loci (rs174547 in fatty acid desaturase 1 (FADS1), rs2338104 near mevalonate kinase/methylmalonic aciduria, cobalamin deficiency, cblB type (MVK/MMAB) and rs10468017 near hepatic lipase (LIPC)) influence the plasma concentrations of high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG). However, there are few reports on the associations between these polymorphisms and plasma lipid concentrations in Chinese individuals. This study aimed to evaluate the associations between these three polymorphisms with HDL-C and TG concentrations, as well as coronary heart disease (CHD) susceptibility in Chinese individuals.</p><p><b>METHODS</b>We conducted a population-based case-control study in Chinese individuals to evaluate the associations between these three polymorphisms and HDL-C and TG concentrations, and also evaluated their associations with susceptibility to CHD. Genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism assays and TaqMan genotyping assays.</p><p><b>RESULTS</b>We found significant differences in TG and HDL-C concentrations among the TT, TC and CC genotypes of FADS1 rs174547 (P=0.017 and 0.003, respectively, multiple linear regression). The CC variant of rs174547 was significantly associated with hyperlipidemia compared with the TT variant (adjusted odds ratio (OR)=1.71, 95% confidence intervals (CI): 1.16-2.54). The FADS1 rs174547 CC variant was also associated with significantly increased CHD risk compared with the TT and TC variant (adjusted OR=1.53, 95%CI: 1.01-2.31), and the effect was more evident among nonsmokers and females. The polymorphisms rs2338104 and rs10468017 did not significantly influence HDL-C or TG concentrations in this Chinese population.</p><p><b>CONCLUSION</b>rs174547 in FADS1 may contribute to the susceptibility of CHD by altering HDL-C and TG levels in Chinese individuals.</p>

Effects of heme oxygenase-1 gene modulated mesenchymal stem cells on vasculogenesis in ischemic swine hearts / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mesenchymal stem cells (MSCs) transplantation may partially restore heart function in the treatment of acute myocardial infarction (AMI). The aim of this study was to explore the beneficial effects of MSCs modified with heme xygenase-1 (HO-1) on post-infarct swine hearts to determine whether the induction of therapeutic angiogenesis is modified by the angiogenic cytokines released from the implanted cells.</p><p><b>METHODS</b>In vitro, MSCs were divided into four groups: (1) non-transfected MSCs (MSCs group), (2) MSCs transfected with the pcDNA3.1-Lacz plasmid (Lacz-MSCs group), (3) MSCs transfected with pcDNA3.1-hHO-1 (HO-1-MSCs group), and (4) MSCs transfected with pcDNA3.1-hHO-1 and pretreatment with an HO inhibitor, tin protoporphyrin (SnPP) (HO-1-MSCs + SnPP group). Cells were cultured in an airtight incubation bottle for 24 hours, in which the oxygen concentration was maintained at < 1%, followed by 12 hours of reoxygenation. After hypoxia/reoxygen treatment, ELISA was used to measure transforming growth factor (TGF-β) and fibroblast growth factor (FGF-2) in the supernatant. In vivo, 28 Chinese mini-pigs were randomly allocated to the following treatment groups: (1) control group (saline), (2) Lacz-MSCs group, (3) HO-1-MSCs group, and (4) HO-1-MSCs + SnPP group. About 1 × 10(7) of autologous stem cells or an identical volume of saline was injected intracoronary into porcine hearts 1 hour after MI. Magnetic resonance imaging (MRI) assay and postmortem analysis were assessed four weeks after stem cell transplantation.</p><p><b>RESULTS</b>Post hypoxia/reoxygenation in vitro, TGF-β in the supernatant was significantly increased in the HO-1-MSCs ((874.88 ± 68.23) pg/ml) compared with Lacz-MSCs ((687.81 ± 57.64) pg/ml, P < 0.001). FGF-2 was also significantly increased in the HO-1-MSCs ((1106.48 ± 107.06) pg/ml) compared with the Lacz-MSCs ((853.85 ± 74.44) pg/ml, P < 0.001). In vivo, at four weeks after transplantation, HO-1 gene transfer increased the capillary density in the peri-infarct area compared with the Lacz-MSCs group (14.24 ± 1.66/HPFs vs. 11.51 ± 1.34/HPFs, P < 0.001). Arteriolar density was also significantly higher in HO-1-MSCs group than in the Lacz-MSCs group (7.86 ± 2.00/HPFs vs. 6.45 ± 1.74/HPFs, P = 0.001). At the same time, the cardiac function was significantly improved in the HO-1-MSCs group compared with the Lacz-MSCs group ((53.17 ± 3.55)% vs. (48.82 ± 2.98)%, P < 0.05). However, all these effects were significantly abrogated by SnPP.</p><p><b>CONCLUSION</b>MSCs provided a beneficial effect on cardiac function after ischemia/reperfusion by the induction of therapeutic angiogenesis, and this effect was amplified by HO-1 overexpression.</p>

Efficiently tracking of stem cells in vivo using different kinds of superparamagnetic iron oxide in swine with myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Superparamagnetic iron oxide (SPIO) particles have shown much promise as a means to visualize labeled cells using molecular magnetic resonance imaging (MRI). Micrometer-sized superparamagnetic iron oxide (MPIO) particles and nanometer-sized ultrasmall superparamagnetic iron oxide (USPIO) are two kinds of SPIO widely used for monitoring stem cells migration. Here we compare the efficiency of two kinds of SPIO during the use of stem cells to treat acute myocardial infarction (AMI).</p><p><b>METHODS</b>An AMI model in swine was created by 60 minutes of balloon occlusion of the left anterior descending coronary artery. Two kinds of SPIO particles were used to track after intracoronary delivered 10(7) magnetically labeled mesenchymal stem cells (MR-MSCs). The distribution and migration of the MR-MSCs were assessed with the use of 3.0T MR scanner and then the results were confirmed by histological examination.</p><p><b>RESULTS</b>MR-MSCs appeared as a local hypointense signal on T₂*-weighted MRI and there was a gradual loss of the signal intensity after intracoronary transplantation. All of the hypointense signals in the USPIO-labeled group were found on T₂*-weighted MRI, contrast to noise ratio (CNR) decreased in the MPIO-labeled group (16.07 ± 5.85 vs. 10.96 ± 1.34) and USPIO-labeled group (11.72 ± 1.27 vs. 10.03 ± 0.96) from 4 to 8 weeks after transplantation. However, the hypointense signals were not detected in MPIO-labeled group in two animals. MRI and the results were verified by histological examination.</p><p><b>CONCLUSIONS</b>We demonstrated that two kinds of SPIO particles in vitro have similar labeling efficiency and viability. USPIO is more suitable for labeling stem cells when they are transplanted via a coronary route.</p>

Transplantation of 5-azacytidine treated cardiac fibroblasts improves cardiac function of infarct hearts in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cellular cardiomyoplasty by transplantation of various cell types has been investigated as potential treatments for the improvement of cardiac function after myocardial injury. A major barrier for the clinical application of cell transplantation is obtaining sufficiently large quantities of suitable cells. Allogeneic cellular cardiomyoplasty may provide an alternative source of abundant, transplantable, myogenic cells by in vitro manipulation of cardiac fibroblasts using chemicals including 5-azacytidine. This study evaluated cardiomyogenic differentiation of cardiac fibroblasts, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function.</p><p><b>METHODS</b>Primary cardiac fibroblasts from neonatal rats were treated with 5-azacytidine (10 µmol/L) or control. Treatment of 5-azacytidine caused myogenic differentiation of cultured cardiac fibroblasts, as defined by elongation and fusion into multinucleated myotubes with sarcomeric structures as identified by electron microscopy, and positive immunostaining for cardiac specific proteins, troponin I and β-myosin heavy chain (β-MHC) and the gap junction protein connexin 43. The myogenic cells (1.0 × 10⁶) were transplanted into the infarcted myocardium 2 weeks after coronary artery occlusion.</p><p><b>RESULTS</b>By 1 month after transplantation, the converted fibroblasts gave rise to a cluster of cardiac-like muscle cells that in the hearts occupied a large part of the scar with positive immunostaining for the myogenic proteins troponin I and β-MHC. Engrafted cells also expressed the gap junction protein connexin 43 in a disorganized manner. There was no positive staining in the control hearts treated with injections of culture medium. Heart function was evaluated at 6 weeks after myocardial injury with echocardiographic and hemodynamic measurements. Improvement in cardiac function was seen in the hearts transplanted with the 5-azacytidine-treated cardiac fibroblasts which was absent in the hearts treated with control.</p><p><b>CONCLUSION</b>The 5-azacytidine has a unique capacity to induce myogenesis in cardiac fibroblasts in vitro and transplantation of cardiac-like muscle cells into ventricular scar tissue improves myocardial function.</p>

Effects of autologous mesenchymal stem cells transfected with heme oxygenase-1 gene transplantation on ischemic Swine hearts / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effect of intracoronary transfer of autologous HO-1 overexpressed MSCs in porcine model of myocardial ischemia (1 h)/reperfusion.</p><p><b>METHODS</b>Apoptosis was assayed and cytokine concentrations in supernatant were measured in cells exposed to hypoxia-reoxygen in vitro. In vivo, Chinese male mini-pigs were allocated to the following treatment groups: control group (saline), MSCs group (MSCs), MSCs transfected with pcDNA3.1-nHO-1 (HO-1-MSCs). 1 x 10(7) of autologous stem cells or identical volume of saline was injected intracoronary into porcine hearts 1 h after ischemia. MRI assay and postmortem analysis were assessed 3 months after stem cell transplantation.</p><p><b>RESULTS</b>In vitro, cell apoptosis rate post hypoxia-reoxygen was significantly reduced in HO-1-MSCs group (30.30% +/- 7.64%) compared with that in MSCs group (56.93% +/- 4.68%, P < 0.001) and LacZ-MSCs group (55.88% +/- 4.38%, P < 0.001), VEGF was also significantly upregulated in HO-1-MSCs group [(768.44 +/- 78.38) pg/ml] compared with that in MSCs group [(555.27 +/- 67.67) pg/ml, P < 0.001] and LacZ-MSCs group [(522.97 +/- 71.45) pg/ml, P < 0.001]. In vivo, cardiac function was significantly improved in both MSCs transplantation groups compared to saline group (all P < 0.05 vs.saline) and the left ventricular ejection fraction was significantly higher in HO-1-MSCs group compared with that in MSCs group at 3 months after transplantation (53.50% +/- 2.09% vs. 49.54% +/- 2.74%, P = 0.017), capillary density in the peri-infarct area was also significantly higher in HO-1-MSC group than that in MSCs group [(14.59 +/- 2.39)/HPF vs. (11.78 +/- 2.48)/HPF, P = 0.033].</p><p><b>CONCLUSIONS</b>Efficacy of HO-1 overexpressed MSCs on improving cardiac function and promoting angiogenesis was greater than those by MSCs in this porcine ischemia/reperfusion model.</p>

Therapeutic effects of magnetically labeled mononuclear and mesenchymal stem cells transplantation in a swine myocardial infarction model assessed by magnetic resonance imaging / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effects of magnetically labeled mononuclear stem cells (MR-MNC) and mesenchymal stem cells (MR-MSC) transplantation in a swine acute myocardial infarction (AMI) model by MR imaging.</p><p><b>METHODS</b>AMI model was established in swines by balloon occlusion of the left anterior descending coronary artery, 10(7) autologous MR-MSC (n = 7), MR-MNC (n = 6) or PBS (n = 6) were delivered via intracoronary infusion within 1 week after AMI [(4.8 +/- 1.3) days]. Changes of infarct size and cardiac function were assessed with the use of 3.0T MR scanner before AMI, at 1 and 8 weeks post AMI.</p><p><b>RESULTS</b>Magnetically labeled stem cells could be identified in the region of AMI by cardiac MR imaging. Eight weeks post transplantation, infarct size was significantly reduced in MR-MSC transplantation group (8.5% +/- 0.5% vs. 24.7% +/- 3.1%, P < 0.05) and in MR-MNC transplantation (12.3% +/- 1.5% vs. 26.1% +/- 1.5%, P < 0.05) while infarct size remained unchanged in PBS group (P > 0.05) compared to values at 1 week post AMI, left ventricular ejection fraction (LVEF) was also significantly higher in MR-MSC transplantation group (56.9% +/- 1.3% vs. 40.7% +/- 2.0%, P < 0.05) and MR-MNC transplantation group (52.8% +/- 1.4% vs. 41.9% +/- 3.3%, P < 0.05) compared to LVEF at 1 week post AMI. LVEF increase was more significant in swines received MR-MSC transplantation than MR-MNC transplantation (16.2% +/- 1.2% vs. 10.9% +/- 3.0%, P < 0.05). Prussian blue staining identified stem cells in corresponding myocardial regions with as by MRI. Western blot analysis demonstrated that cardiac expressions of myosin heavy chain (MHC) in MR-MSC group (100.3 +/- 5.5) and in MR-MNCs group (95.5 +/- 4.2) were significantly higher than that in PBS group (75.7 +/- 5.7, P < 0.05), myocardial troponin T (cTNT) expression in MR-MSC group (124.0 +/- 5.8) and MR-MNC group (118.4 +/- 4.4) were also significantly higher than in PBS group (93.3 +/- 3.9, P < 0.05) while MMP2/TIMP1 ratios in MR-MSC group (0.6 +/- 0.1) and MR-MNC group (0.6 +/- 0.1) were significantly lower than that in PBS group (4.2 +/- 0.2, P < 0.05).</p><p><b>CONCLUSIONS</b>Magnetically labeled MR-MSC and MR-MNC homed to heart post myocardial infarction and reduced infarct size, improved cardiac function. MR-MSC is superior to MR-MNC on improving cardiac function.</p>

Transplantation of magnetically labeled mesenchymal stem cells improves cardiac function in a swine myocardial infarction model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mesenchymal stem cells (MSCs) transplantation provides a new approach for myocardial repair. However, many important fundamental questions about MSCs transplantation remain unanswered. There is an urgent need to identify MSCs from the beating heart and analyze the efficacy of this new approach. This study aimed to localize the magnetically labeled MSCs (MR-MSCs) and monitor the restorative effects of MR-MSCs with magnetic resonance (MR) imaging.</p><p><b>METHODS</b>Acute myocardial infarction (AMI) was created in swine by a balloon occlusion of the left anterior descending coronary artery. Cells were delivered via intracoronary infusion after myocardial infarction. Infarct size change and cardiac function were assessed with 3.0T MR scanner. The results were then confirmed by histological and western blot analysis. All statistical procedures were performed with Systat (SPSS version 12.01).</p><p><b>RESULTS</b>A total of 26 swine were divided into four groups (sham-operated group, n=6; AMI group with PBS transplantation, n=6; labeled MSCs group, n=7; unlabeled MSCs group, n=7). MSCs, MR-MSCs (10(7) cells) or PBS were delivered by intracoronary injection after MI and serial cardiac MR imaging studies were performed at 0, 4 and 8 weeks after transplantation. MR imaging demonstrated MI size decreased after MSCs transplantation in labeled and unlabeled groups, however, increases were seen in the AMI group at 8 weeks after MI. The left ventricular ejection fraction (LVEF) was slightly increased in the AMI group ((41.87+/-2.45)% vs (39.04+/-2.80)%, P>0.05), but significantly improved in the MR-MSCs group ((56.85+/-1.29)% vs (40.67+/-2.00)%, P<0.05) and unlabeled group ((55.38+/-1.07)% vs (41.78+/-2.08)%, P<0.05) at 8 weeks after treatment. MR-MSCs were further confirmed by Prussian blue and immunofluorescent staining. Western blot analysis demonstrated that there was an increased expression of cardiomyocyte markers such as myosin heavy chain and troponin T in the MSCs treatment groups and the ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase 1 decreased in the labeled group and unlabeled group compared with the AMI group and sham-operated group.</p><p><b>CONCLUSION</b>Transplanted MR-MSCs can regenerate new myocardium and prevent remolding in an MI model at 2-month follow-up and represent a preferred method to better understand the mechanisms of stem cell therapy in future clinical studies.</p>

Prognostic value of devated baseline C-reactive protein and interleukin-6 levels on the vascular complications in percutaneous coronary intervention / 中华急诊医学杂志

Objective To investigate whether elevated pre-procedural C-reactive protein (CRP) and Interleukin-6 (IL-6) concentrations may be relevant to early outcome in patients undergoing PCI.Method 100 consecutive patients undergoing pereutaneuous coronary intervention (PCI) were included in our study.Peripheral blood samples for CRP and IL-6 testing were withdrawn before PCI.Acute vascular complications resulted from PCI were determined by subsequently coronary angiography.The early coronary events during hospitalization were clinically followed.Results Thirty patients developed acute vessel occlusion,and another one developed subacute coronary thrombosis at 2 days after PCI.Increased levels of CRP correlated well with the occurrence of vascular complications as regards the significant difference existing amongⅠvsⅢandⅠvsⅣquartile groups,P

A study of human annexin V derivative: its effects of anticoagulation and antithrombosis / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of a new anticoagulant, annexin V derivative (AND) on anticoagulation and antithrombosis.</p><p><b>METHODS</b>High and low doses of AND were given to rabbits (groups 1 and 2 respectively) by intravenous (iv) bolus injections followed by half the respective AND doses by iv infusion over 2 hours. Control groups were iv given heparin (group 3) and saline (group 4) of the same volume and procedure as that in group 1 and 2. Blood cell count, activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen level were examined before and 15, 30 and 60 min after iv bolus and 2 hours after the end of iv infusion. A 3.0 mm x 15 mm balloon was put into femoral artery to induce endothelial denudation 15 min after IV bolus and the blood pressure of femoral artery was monitored until the pulse pressure recorded 0 mm Hg when the vessel was occluded completely by a thrombus. The femoral arteries were collected and the thrombi were stripped off for measuring their lengths, wet and dry weights.</p><p><b>RESULTS</b>Anticoagulation parameters: APTT at 15 min after iv bolus in AND group was significantly longer than that in group 4 (P < 0.05) but shorter than that in group 3 (P < 0.05); APTT and TT in group 3 were significantly longer than those in groups 1, 2 and 4. Fibrinogen: 0.70 mg/kg AND may decrease fibrinogen. Antithrombosis values: the wet and dry weights in AND groups were significantly lighter than those in group 3 and 4 (P < 0.05). The dry weight in high-dose AND group was remarkably lighter than that in low-dose group (P = 0.029). The length of thrombus in low-dose AND group was remarkably shorter than that in group 4 (P = 0.013), but not for group 3 (P > 0.05). It was remarkably shorter in high-dose AND group than in both group 3 (P < 0.001) and 4 (P = 0.015). The time when pulse pressure equaled to 0 was longer in AND group than in group 4 (P < 0.05), but not in 3.</p><p><b>CONCLUSION</b>AND is an effective anticoagulant and antithrombosis agent, the highest anticoagulation effect occurs at 15 min after IV bolus. Its anticoagulation effect is not more potent than that of standard heparin, while antithrombosis capacity is more effective. AND in treating thrombosis clinically might be promising.</p>