A circRNA-miRNA-mRNA network analysis underlying pathogenesis of human heart failure / 老年心脏病学杂志（英文版）

BACKGROUND@#The molecular mechanisms of heart failure (HF) are still poorly understood. Circular RNA (circRNA) has been discovered in the heart in increasing numbers of studies. The goal of this research is to learn more about the potential roles of circRNAs in HF.@*METHODS & RESULTS@#We used RNA sequencing data to identify the characteristics of circRNAs expressed in the heart and discovered that the majority of circRNAs screened were less than 2000 nt. Additionally, chromosomes One and Y had the most and least number of circRNAs, respectively. After excluding duplicate host genes and intergenic circRNAs, a total of 238 differentially expressed circRNAs (DECs) and 203 host genes were discovered. However, only four of the 203 host genes of DECs were examined in HF differentially expressed genes. Another study used Gene Oncology analysis of DECs host genes to elucidate the underlying pathogenesis of HF, and it found that binding and catalytic activity accounted for a large portion of DECs. Immune system, metabolism, and signal transduction pathways were significantly enriched. Furthermore, 1052 potentially regulated miRNAs from the top 40 DECs were collected to build a circRNA-miRNA network, and it was discovered that 470 miRNAs can be regulated by multiple circRNAs, while others are regulated by a single circRNA. In addition, a comparison of the top 10 mRNAs in HF and their targeted miRNAs revealed that DDX3Y and UTY were regulated by the most and least circRNA, respectively.@*CONCLUSION@#These findings demonstrated circRNAs have species and tissue specific expression patterns; while circRNA expression is independent on host genes, the same types of genes in DECs and DEGs worked in HF. Our findings would contribute to a better understanding of the critical roles of circRNAs and lay the groundwork for future studies of HF molecular functions.

Feasibility of echocardiography-guided repeated intraventricular blood sampling in mice / 中华心血管病杂志

Objective: To investigate the feasibility of echocardiography-guided closed-chest repeated intraventricular blood sampling in mice, and to clarify the maximum blood volume that can be collected by this method, and whether the method can be used for long-term repeated blood collection in mice. Methods: Twenty-four male C57BL/6J mice (10-14 weeks old) were divided into the terminal experiment group (n=4, for investigating the maximum blood amount that could be sampled at one time), the repeated 0.5 ml blood collection group (n=10, sampling 0.5 ml whole blood each time, once every two days for consecutive 4 weeks), and the repeated 0.75 ml blood collection group (n=10, sampling 0.75 ml whole blood each time, once every two days for consecutive 4 weeks). High-frequency echocardiography was used to display the largest section of the left ventricle, guiding the insulin syringe needle through the thorax into the left ventricle for blood collection. In the repeated 0.5 ml blood collection group, echocardiography was used to detect the cardiac structure and function before blood collection, three minutes after blood collection, and one week after the last (the 14th) blood collection. Results: We successfully performed echocardiography-guided closed-chest intraventricular blood sampling, with an average operating time (88±19)s per mouse, and a maximum blood volume (1.43±0.11)ml per mouse. In the repeated 0.5 ml blood collection group, heart rate, left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-diastolic dimension and left ventricular posterior wall end-diastolic thickness remained uncganged before the first blood collection and after 4 weeks of repeated blood collection (all P>0.05). No death in the repeated 0.5 ml blood collection group. However, in the 0.75 ml blood collection group, two mice died before the end point. Conclusions: The echocardiography-guided closed-chest intraventricular blood sampling is a safe, minimally invasive, convenient and efficient method, and can be used repeatedly for long-term blood collection in mice.

Efficacy of autologous bone marrow-derived cells transfer for patients with chronic ischemic heart disease: a meta-analysis / 中华心血管病杂志

<p><b>OBJECTIVE</b>We aimed to perform a meta-analysis of clinical trials on the efficacy of autologous bone marrow-derived cells (BMCs) transfer for patients with chronic ischemic heart disease.</p><p><b>METHODS</b>We searched MEDLINE, EMBASE, and Cochrane database through September 2009. Eligible studies were randomized controlled trials of autologous BMCs infusion in patients with chronic ischemic heart disease. We gathered information about left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and death, and did a random-effect meta-analysis to obtain summary effect estimates for outcomes. The pooled analyses were performed and forest plots were generated with RevMan 5.0 software. Heterogeneity was assessed by meta-regression with STATA 10.0 software. Additionally, subgroup analysis was performed to compare the effect of intracoronary BMCs transfer with intramyocardial cell injection on LVEF.</p><p><b>RESULTS</b>Eleven trials with 490 participants were identified. There were 268 patients in BMCs group, and 222 in control group. In control group, the patients received saline injection or autologous plasma injection or no injection. BMCs transfer was performed via intracoronary transfer or intramyocardial injection. Compared with controls, BMCs transfer significantly improved LVEF by 4.63% (95%CI 2.42 to 6.84; P < 0.01). BMCs transfer was also associated with significant reductions in LVEDV (standardized mean difference -0.55, 95%CI -0.94 to -0.17, P = 0.005) and LVESV (standardized mean difference -0.45, 95%CI -0.73 to -0.17, P = 0.002). In addition, BMCs treatment was associated with a significant effect on death (OR 0.42, 95%CI 0.18 to 1.01, P = 0.05). Subgroup analysis indicated that intramyocardial cell injection was preferred due to its more significant improvement of LVEF than intracoronary cell therapy. Meta-regression suggested the existence of a negative association between baseline LVEF and LVEF change.</p><p><b>CONCLUSION</b>BMCs infusion is associated with a significant improvement in LVEF, and an attenuation of left ventricular remodeling.</p>

Acute hyperenhancement on delayed contrast-enhanced magnetic resonance imaging is the characteristic sign after coronary microembolization / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Detection of coronary microembolization is of clinical importance for patient management and prediction of long-term outcome. However, there are few studies of the changes of magnetic resonance imaging after coronary microembolization. This study was designed to investigate the imaging of the left ventricle using delayed contrast enhanced magnetic resonance imaging as well as the left ventricular ejection fraction after coronary microembolization in animal models.</p><p><b>METHODS</b>Eight miniswine, of either sex (body weight 21-25 kg), were used to make the coronary microembolization model. After coronary angiography, a 2.8F infusion catheter was placed in the left anterior descending artery with the tip located between the second and third diagonal branches. Microspheres with the diameter of 42 microm and mean dosage of 1.2 x 10(5) were selectively infused into the left anterior descending artery. First pass and stressed first pass perfusion scan were performed after cine images were acquired. Then a second bolus of 0.15 mmol/kg gadolinium DTPA was given at a rate of 2 ml/s. Ten minutes later, delayed contrast enhanced magnetic resonance images of the left ventricular wall were evaluated. Serum changes of tumor necrosis factor alpha (TNF-alpha) were evaluated by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Hypoenhancement was not observed at first pass perfusion at the anterior wall of the left ventricle. Hyperenhancements of the anterior-septal and anterior wall of the left ventricle was in evidence on delayed enhancement images 6 hours after microembolization and disappeared one week later. The characteristic change of coronary microembolization on delayed contrast enhanced magnetic imaging was non-enhanced regions within the hyperenhancement zone. Left ventricular ejection fraction measured by magnetic resonance imaging decreased significantly from 0.451 +/- 0.063 at baseline to 0.362 +/- 0.070 at the sixth hour (P < 0.01), and recovered to 0.431 +/- 0.053 one week later (P < 0.01 vs 6th hour). Compared with baseline values, the left ventricular end systolic volume enlarged significantly at 6th hour and at one week after microembolization (P < 0.05 and P < 0.01 respectively). Serum TNF-alpha increased significantly at 6th hour (22.62 +/- 6.96) pg/ml compared with baseline (16.83 +/- 3.45) pg/ml (P < 0.05) and it further increased to (27.44 +/- 3.97) pg/ml at one week after coronary microembolization and was significantly higher than that at baseline (P < 0.01).</p><p><b>CONCLUSIONS</b>On delayed contrast enhanced magnetic resonance imaging, hyperenhancement of the anterior-septal and anterior wall of the left ventricle show at 6th hour but not at one week after coronary microembolization. This might represent the characteristic imaging after coronary microembolization. The left ventricular ejection fraction decreased at 6th hour and recovered one week later after coronary microembolization. Although impairment of left ventricular function could be recovered at 1 week after coronary microembolization, the left ventricular remodeling process still continued in concert with continuously elevation of serum TNF-alpha.</p>

Intracoronary and hypodermic injection of granulocyte colony-stimulating factor improved cardiac function in Swine with chronic myocardial ischemia / 中华心血管病杂志

<p><b>OBJECTIVES</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Systematic review on safety of intracoronary autologous bone marrow stem cells transfer in patients with acute myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To estimate the safety of intracoronary autologous bone marrow stem cells (BMSC) transfer in patients with acute myocardial infarction.</p><p><b>METHODS</b>A systematic literature search of PubMed, MEDLINE, Cochrane EBM, BIOSIS, EMBASE and Chinese Journal Full-text Database between January 1990 and May 2007, was performed. Inclusion criteria required that patients received intracoronary BMSC transfer after coronary reperfusion therapy for primary acute myocardial infarction; study design involved patient randomization and matching placebo group as well as detailed safety data with more than 3 months follow-up results.</p><p><b>RESULTS</b>A total of 5 trials with 620 patients were available for analysis. The pooled statistics showed similar results between BMSC and placebo groups in terms of occurrence of the individual clinical adverse events and the combined endpoint death, recurrence of myocardial infarction, or revascularization procedures. The combined endpoint death, recurrence of myocardial infarction, revascularization procedures, or rehospitalization for heart failure was significantly reduced in the BMSC group compared with the control group at more than one year follow-up (OR = 0.45, 95%CI 0.28 - 0.74, P = 0.002). Likewise, the occurrence of revascularization and the combined endpoint death, recurrence of myocardial infarction, or revascularization procedures were significantly reduced when BMSC transplantation was performed between 4 and 7 days after primary percutaneous coronary intervention (PCI) (OR = 0.60, 95%CI 0.37 - 0.97, P = 0.04; OR = 0.58, 95%CI 0.37 - 0.91, P = 0.02, respectively). In contrast, there was a significant increase in the combined endpoint revascularization and recurrence of myocardial infarction when BMSC transplantation was performed within 24 hours after PCI (OR = 2.56, 95%CI 1.03 - 6.34, P = 0.04).</p><p><b>CONCLUSIONS</b>Post PCI intracoronary autologous BMSC transplantation in patients with acute myocardial infarction is safe, especially in patients received BMSC transplantation between 4 and 7 days after primary PCI than patients received BMSC transplantation within 24 hours post PCI.</p>

Hyperinsulinemia induced immune maturation of human monocyte derived dendritic cells: bridging between diabetes and atherosclerosis / 中华心血管病杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Hyperinsulinemia contributed to atherosclerosis via stimulating immune maturation of MoDCs via both PI3K and MAPK pathways.</p>

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 / 中华心血管病杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

In vivo cardiac magnetic resonance imaging of superparamagnetic iron oxides-labeled mesenchymal stem cells in swines / 中华心血管病杂志

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Transplantation of autologous bone marrow mononuclear cells on patients with idiopathic dilated cardiomyopathy: early results on effect and security / 中华心血管病杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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].</p><p><b>CONCLUSIONS</b>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.</p>

Observation on the safety: clinical trail on intracoronary autologous bone marrow mononuclear cells transplantation for acute myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the safety of autologous bone marrow mononuclear cell (BM-MNCs) transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Intracoronary transplantation of autologous BM-MNCs in the acute phase after AMI is feasible and seems safe in the 30 months of follow-up.</p>

Effects and mechanism of hyperglycemia on development and maturation and immune function of human monocyte derived dendritic cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Impact of pathogen burden on in-stent restenosis in patients after coronary stent implantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although some certain infectious pathogens could be detected in the patients with coronary artery disease, the roles of these infectious factors in the development of coronary artery diseases remain largely unknown. Since the number of infectious pathogens has been argued to be relative to the coronary artery diseases, we therefore examined whether there is a link between the number of infections and the incidence of in-stent restenosis after stent implantation.</p><p><b>METHODS</b>One hundred and eighty-one patients were enrolled in this study. Infectious pathogens including serum anti-Chlymydia pneumoniae, cytomegalovirus, Helico pylori, human herpes simplex virus-1, human herpes simplex virus-2 antibodies and hepatitis B virus antigen were measured in all patients before coronary stent implantation. Coronary angiography was performed before, immediately after and 6 months after stent implantation.</p><p><b>RESULTS</b>Restenosis rate 6 months post stent implantation was similar in patients with low pathogen burden (< 3 pathogens, 33.3%) to those with high pathogen burden (> or = 3 pathogens, 29.1%).</p><p><b>CONCLUSIONS</b>Previous infections with Chlymydia pneumoniae, cytomegalovirus, Helico pylori, human herpes simplex virus-1, human herpes simplex virus-2 and hepatitis B virus do not contribute to the incidence of restenosis after stent implantation.</p>