Objective To investigate the effects of activator protein-1(AP-1)decoy oligodeoxynucleotides (ODNs)on the myocardial fibrosis induced by angiotension Ⅱ(Ang Ⅱ)in vitro.Methods CFs of neonatal Spra- gue-Dawley(SD)rats were isolated by trypsin digestion method.CFs were co-cultured with 10~(-7)mol/L Ang Ⅱ in the presence of different concentration of activator protein-1(AP-1)decoy ODNs or mutational AP-1 decoy ODNs for 24 h.Collagen synthesis was assessed by hydroxyproline and the mRNA expression of collagen Ⅰ,collagen Ⅲ.Results The concentration of hydroxyproline increased significantly after treated by 10~(-7)mol/L Ang Ⅱ;decoy ODNs on the range of 10-200 nmol/L dose dependently decrease synthesis of collagen;Ang Ⅱ stimulates mRNA expression of collagen Ⅲ(1.04?0.07 vs 1.63?0.071,n=3,P

BACKGROUNDWhether an addition of OAC to double antiplatelet therapy for patients with an indication of chronic oral anticoagulation undergoing PCI-S may improve clinical outcomes is still debated. This meta-analysis aimed to update and re-compare the benefits and risks of triple antithrombotic therapy (TT) with double anti-platelet therapy (DAPT) after in patients who requiring oral anticoagulation after percutaneous coronary interventions with stenting (PCI-s).

METHODSTen reports of observational retrospective or prospective studies were retrieved, including a total of 6296 patients, follow-up period ranging from 1 year to 2 years.

RESULTSBaseline characteristics were similar in both groups. The main finding of this study is the overall incidence of major adverse cardiovascular events (MACE), myocardial infarction (MI) and stent thrombosis was comparable between two groups. Patients with TT was associated with significant reduction in ischemic stroke (OR: 0.27; 95%CI: 0.13 - 0.57; P = 0.0006) as compared to DAPT. We reaffirmed triple therapy significantly increased the risk of major bleeding (OR: 1.47; 95%CI: 1.22 - 1.78; P < 0.0001) and minor bleeding (OR: 1.55; 95%CI: 1.07 - 2.24; P = 0.02).

CONCLUSIONSTriple therapy is more efficacious in reducing the occurrence of ischemic stroke in PCI-s patients with an indication of chronic oral anticoagulation (OAC), compared with DAPT. However, it significantly increased major and minor risk of bleeding. It is imperative that further prospective randomized controlled trials are required to defne the best therapeutic strategy for patients with an indication of chronic OAC undergoing PCI-s.

Aged ; Anticoagulants ; therapeutic use ; Drug Therapy, Combination ; Female ; Fibrinolytic Agents ; administration & dosage ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; administration & dosage ; Publication Bias ; Stents

BACKGROUNDRecent studies indicate that bone marrow-derived cells may significantly contribute to atherosclerosis, post-angioplasty restenosis and transplantation-associated vasculopathy. The responsible bone marrow (BM) cells and mechanisms regulating the mobilization of these cells are currently unclear. The purpose of this study was to investigate the expression of granulocyte colony-stimulating factor (G-CSF) on injured arteries and its effects on mesenchymal stem cells (MSCs) differentiation into vascular smooth muscle cells (VSMCs) in the process of vascular remodeling.

METHODSBalloon-mediated vascular injury was established in female rats (n = 100) which received radioprotective whole female BM cells by tail vein injection and male MSCs through a tibial BM injection after lethal irradiation. The injured and contralateral carotid arteries were harvested at 3, 7, 14 and 28 days after treatment.

RESULTSMorphometric analysis indicated that intima to media area-ratio (I/M ratio) significantly increased at 28 days, 0.899 ± 0.057 (P < 0.01), compared with uninjured arteries. Combining fluorescence in situ hybridization (FISH) and immunohistochemical analysis showed that a significant number of the neointimal cells derived from MSCs, (45.2 ± 8.5)% at 28 days (P = 0.01), compared with (23.5 ± 6.3)% at 14 days. G-CSF was induced in carotid arteries subject to balloon angioplasty (fold mRNA change = 8.67 ± 0.63 at three days, relative G-CSF protein = 0.657 ± 0.011 at three days, P < 0.01, respectively, compared with uninjured arteries). G-CSF was chemotactic for MSCs but did not affect the differentiation of MSCs into smooth-muscle-like cells.

CONCLUSIONIncreased expression of G-CSF by injured arteries plays an essential role in contribution to recruitment and homing of MSCs to the site of the arterial lesion.

Angioplasty, Balloon ; Animals ; Blotting, Western ; Carotid Arteries ; surgery ; Cell Differentiation ; Cell Movement ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Female ; Granulocyte Colony-Stimulating Factor ; metabolism ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Mesenchymal Stromal Cells ; cytology ; Myocytes, Smooth Muscle ; cytology ; Neointima ; surgery ; therapy ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular System Injuries ; surgery ; therapy

OBJECTIVETo evaluate the impact of insulin resistance (IR) on prognosis in non-diabetic acute coronary syndrome patients.

METHODSIn this prospective study, we enrolled 332 non-diabetic patients suffering from acute coronary syndrome. The patients were divided into three groups by HOMA-IR which calculated by formula: low HOMA-IR group (HOMA-IR < 2), 44 cases; moderate HOMA-IR group (2 ≤ HOMA2-IR < 6), 99 cases; high HOMA-IR group (HOMA ≥ 6) with HOMA index, 179 cases. The in-hospital medical records of patients were compared, and all patients were followed up for one year after discharge.

RESULTSIncidence of hypertension (P = 0.013), dyslipidemia (P < 0.001), faster resting heart rate (P < 0.001) and number of triple vessel coronary artery disease (P = 0.017) in high HOMA-IR group were significantly higher than in low and moderate HOMA-IR group. During follow-up, the major end-point events increased in proportion to IR grade: 64.3% (26/44) in the high HOMA-IR group, 54.7% (52/99) in moderate HOMA-IR group and 41.3% (74/199) in low HOMA-IR group (P = 0.034). Multivariable logistic regression analysis showed that high sensitivity C reactive protein (OR = 1.012, 95%CI:1.002-1.022, P = 0.022), HOMA-IR (OR = 1.250, 95%CI:1.043-1.497, P = 0.015) , triple vessel coronary artery disease (OR = 5.914, 95%CI:2.947-11.868, P < 0.001) , ischemic changes on ECG (OR = 5.495, 95%CI:2.925-10.324, P < 0.001) and low left ventricular ejection fraction (LVEF ≤ 40%) (OR = 13.205, 95%CI:5.000-34.661, P < 0.001) were independent risk factor for major end-point events during follow-up.

CONCLUSIONSIncreased insulin resistance is linked with poor prognosis of non-diabetic patients with acute coronary syndrome.

Acute Coronary Syndrome ; Aged ; Female ; Follow-Up Studies ; Humans ; Insulin Resistance ; Logistic Models ; Male ; Middle Aged ; Prognosis ; Prospective Studies

OBJECTIVETo investigate the inhibitory effects of AP-1 decoy oligodeoxynucleotides (ODNs) on angiotensin II (AngII)-induced proliferation and collagen synthesis in neonatal rat cardiac fibroblasts (CFs).

METHODSThe CFs of neonatal SD rats were cultured in serum-free medium for 24 h and stimulated with 10(-7) mol/L AngII in the presence of AP-1 decoy ODNs or mutational AP-1 decoy ODNs at varied concentrations. MTT assay was employed for quantitative evaluation of the CF proliferation. Collagen synthesis in the CFs was assessed with hydroxyproline, and the cell cycle distribution determined with flow cytometry (FCM).

RESULTSWith the increase of the concentration of AP-1 decoy ODNs, the absorbance at 490 nm (OD490) of the CFs decreased gradually as shown by MTT assay. Treatment with 100 or 200 nmol/L AP-1 decoy ODNs resulted in significantly lowered OD490 of the CFs as compared with that of AngII group. The concentration of hydroxyproline increased significantly after treatment with 10(-7) mol/L AngII in comparison with the control group (P<0.05). Hydroxyproline concentration in cells treated with 100 or 200 nmol/L AP-1 decoy ODNs was significantly lower than that in the 10(-7) mol/L AngII-treated cells. AP-1 decoy ODNs decreased the cell percentage in S phase and increased hydroxyproline concentration, but increased the percentage of cells in G0/G1 phase. AP-1 decoy ODNs at 100 and 200 nmol/L did not obviously affect AngII-induced CF proliferation and collagen synthesis (P<0.01).

CONCLUSIONAP-1 decoy can inhibit AngII-induced rat CF proliferation and collagen synthesis possibly by affecting the cell cycle distribution.

Angiotensin II ; pharmacology ; Animals ; Animals, Newborn ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Collagen ; biosynthesis ; Dose-Response Relationship, Drug ; Fibroblasts ; cytology ; drug effects ; metabolism ; Flow Cytometry ; Mutation ; Myocardium ; cytology ; metabolism ; Oligodeoxyribonucleotides ; genetics ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Transcription Factor AP-1 ; genetics

OBJECTIVEIt is revealed that circulating fibrocytes are elevated in patients/animals with cardiac fibrosis, and this review aims to provide an introduction to circulating fibrocytes and their role in cardiac fibrosis.

DATA SOURCESThis review is based on the data from 1994 to present obtained from PubMed. The search terms were "circulating fibrocytes " and "cardiac fibrosis ".

STUDY SELECTIONArticles and critical reviews, which are related to circulating fibrocytes and cardiac fibrosis, were selected.

RESULTSCirculating fibrocytes, which are derived from hematopoietic stem cells, represent a subset of peripheral blood mononuclear cells exhibiting mixed morphological and molecular characteristics of hematopoietic and mesenchymal cells (CD34+/CD45+/collagen I+). They can produce extracellular matrix and many cytokines. It is shown that circulating fibrocytes participate in many fibrotic diseases, including cardiac fibrosis. Evidence accumulated in recent years shows that aging individuals and patients with hypertension, heart failure, coronary heart disease, and atrial fibrillation have more circulating fibrocytes in peripheral blood and/or heart tissue, and this elevation of circulating fibrocytes is correlated with the degree of fibrosis in the hearts.

CONCLUSIONSCirculating fibrocytes are effector cells in cardiac fibrosis.

Coronary Disease ; pathology ; Fibroblasts ; physiology ; Fibrosis ; pathology ; Heart Failure ; pathology ; Humans ; Hypertension ; pathology ; Myocardium ; pathology

OBJECTIVE: To explore the value of transthoracic echocardiography (TTE) in transcatheter closure of atrial septal aneurysm (ASA) combined with secoundum-type atrial septal defect (ASD). METHODS: Fourteen patients (3 males and 11 females) who had ASA combined with secoundum-type ASD were diagnosed by TTE or transesophageal echocardiography. The ASA projected to the right atrium in all patients. The width of basilar part was 13 approximately 24 (18.5+/-3.9) mm, and the vertical extent was 7 approximately 11(9.7+/-1.8) mm. Ten patients combined with single hole ASD and 4 patients with multiple hole ASD. Blood shifting from the left atrium to the right atrium was displayed in color Doppler in all patients. All patients were treated by transcatheter closure under the guiding of X fluoroscopy and TTE, and examined with TTE during the follow-up. RESULTS: Transcatheter closure was successfully performed by 14 occluders in all patients. No residual shunt was detected immediately by TTE after the procedure in all patients. During the 6 approximately 12 month follow-up, no residual shunt or occluder shifting was found, the dimensions of the heart became normal in 11 patients (79%) and were significantly decreased in 4. CONCLUSION Transcatheter closure is feasible in patients with ASA combined with secoundum-type ASD, and extra attention must be paid to the specialty. TTE is very important in case selection before transcatheter closure, and it may be used to monitor and guide the procedure during transcatheter closure.
Adult ; Atrial Septum ; Balloon Occlusion ; methods ; Cardiac Catheterization ; Echocardiography ; Female ; Heart Aneurysm ; complications ; therapy ; Heart Septal Defects, Atrial ; complications ; therapy ; Humans ; Male ; Middle Aged ; Ultrasonography, Interventional ; Young Adult

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and site-specific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the −2000 to −1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the −1997 to −1700 and −1091 to −811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.
Binding Sites ; Cholesterol ; Chromatin Immunoprecipitation ; Computational Biology ; Coronary Artery Disease ; Foam Cells* ; Humans ; Interleukin-10* ; Interleukin-33* ; Luciferases ; Macrophages* ; Mutagenesis, Site-Directed ; Phosphorylation ; RNA, Messenger ; Transcription Initiation Site

BACKGROUNDRecently there has been a great deal of interest in the role of serum uric acid (SUA) in atrial fibrillation (AF). The objective of this study was to establish whether there is a relationship between levels of SUA and recurrence of paroxysmal AF after catheter ablation.

METHODSThree hundred and thirty patients diagnosed with paroxysmal AF were analyzed. Patients were categorized into quartiles on the basis of their pre-operative SUA measurement and follow-up, and Kaplan-Meier estimation with a Log-rank test was used for the analysis of the influence of SUA on the recurrence of AF. Pre-procedural clinical variables were correlated with the clinical outcome after ablation using multivariate Logistic analysis. A Cox proportional hazards model was used to estimate the relationship between SUA and the recurrence of AF.

RESULTSAfter a mean follow-up of (9.341 ± 3.667) (range 3.0 - 16.3) months, recurrence rates from the lowest SUA quartile to the highest SUA quartile were 16.0%, 26.4%, 28.3%, and 29.3% respectively (P = 0.014). After adjustment for gender, body mass index (BMI), hypertension, serum levels of high sensitivity C-reactive protein (hsCRP), triglyceride (TG), left atrial diameter (LA), estimated glomerular filtration rate (eGFR), and SUA, there was an increased risk of recurrence in subjects in the highest SUA quartile compared with those in the lowest quartile (hazard ratio 2.804, 95% confidence interval 1.466 - 5.362, P = 0.002). Following multivariate Logistical analysis, SUA was found to be an independent predictor of recurrence (hazard ratio 1.613, 95% confidence interval 1.601 - 1.625, P = 0.014).

CONCLUSIONIn a retrospective study of patients with paroxysmal AF undergoing catheter ablation, elevated preoperative SUA levels were associated with a higher rate of recurrence of AF.

Aged ; Atrial Fibrillation ; blood ; surgery ; Catheter Ablation ; Electrophysiology ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Uric Acid ; blood

BACKGROUNDMutations of the LMNA gene encoding lamin A and C are associated with dilated cardiomyopathy (DCM), conduction system defects and skeletal muscle dystrophy. Here we report a family with a mutation of the LMNA gene to identify the relationship between genotype and phenotype.

METHODSAll 30 members of the family underwent clinical and genetic evaluation. A mutation analysis of the LMNA gene was performed. All of the 12 exons of LMNA gene were extended with polymerase chain reaction (PCR) and the PCR products were screened for gene mutation by direct sequencing.

RESULTSTen members of the family had limb-girdle muscular dystrophy (LGMD) and 6 are still alive. Two patients suffered from DCM. Cardiac arrhythmias included atrioventricular block and atrial fibrillation; sudden death occurred in 2 patients. The pattern of inheritance was autosomal dominant. Mutation c.73C > G (R25G) in exon 1 encoding the globular domains was confirmed in all of the affected members, resulting in the conversion of arginine (Arg) to glycine (Gly).

CONCLUSIONSThe mutation R25G in exon 1 of LMNA gene we reported here in a Chinese family had a phenotype of malignant arrhythmia and mild LGMD, suggesting that patients with familial DCM, conduction system defects and skeletal muscle dystrophy should be screened by genetic testing for the LMNA gene.

Adult ; Cardiomyopathy, Dilated ; genetics ; Exons ; Humans ; Lamin Type A ; genetics ; Muscular Dystrophies, Limb-Girdle ; genetics ; Mutation