Effect of neuregulin-1 on cardiac glucose metabolism in rats with experimental myocardial infarction / 中华心血管病杂志

Objective: To investigate the effect of neuregulin-1(NRG-1) on cardiac glucose metabolism in Sprague Dawley (SD) rats with experimental myocardial infarction (MI). Methods: Adult male SD rats were randomly divided into three groups: the sham-operated group, MI group, and MI+NRG1 group. The rat MI model was established via ligation of the left anterior descending coronary artery. Two weeks after operation, echocardiography was performed, MI rats with left ventricular ejection fraction (LVEF) between 0.3-0.5 were selected and randomly assigned to MI group and MI+NRG-1 group. Rats in MI+NRG-1 group were treated with recombinant human NRG-1β (100 μg/kg) via tail vein at 2 weeks after operation (twice per week for 6 weeks); while rats in sham-operated group and MI group received equal volume of physiological saline. By the end of administration, echocardiography and small animal positron emission tomography (PET) were performed to detect cardiac function and myocardial glucose uptake. Myocardial morphology and collagen volume fraction, cardiomyocyte apoptosis and reactive oxygen species (ROS) production were evaluated by histopathologic analysis. Myocardial pyruvate dehydrogenase (PDH) and citrate synthase (CS) activity, as well as ATP production were detected by commercial kits. The mRNA and protein expression levels of NRG-1, p-ErbB4, and key factors involved in glucose metabolism (including Glut-4, HK2, PDK4, PDH, CS) were detected by quantitative real-time PCR (qRT-PCR) and Western blot assay, respectively. Results: With the MI model successfully established, the left ventricular ejection fraction(LVEF) and left ventricular shortening fraction(LVFS) were significantly lower in MI group and MI+NRG-1 group than that in sham group (both P<0.01), while there was no significant difference between MI group and MI+NRG-1 group(all P>0.05). After 6 weeks of NRG-1β intervention, the LVEF and LVFS were significantly higher in MI+NRG-1 group than in MI group (both P<0.01). By the end of experiment, PET imaging showed that the mean standardized uptake value (SUVmean) were lower in MI+NRG-1 group than in the sham group (4.06±0.28 vs. 5.18±0.37, P<0.01), while significantly higher than that in MI group (4.06±0.28 vs.2.86±0.49, P<0.01). Histopathological analysis showed that compared with MI group, rats in MI+NRG-1 group exhibited significantly decreased left ventricle collagen volume fraction ((7.83±1.24) % vs. (18.31±3.58) %, P<0.01), cardiomyocyte apoptosis((37.98±4.26)% vs. (67.04±5.38)%, P<0.01), and DHE fluorescence intensity(0.057 28±0.007 06 vs. 0.076 94±0.008 46, P<0.01), indicating that NRG-1β could reduce ROS production. PDH activity, CS activity, and ATP production were significantly higher in MI+NRG-1 group than in MI group (all P<0.05). qRT-PCR demonstrated an upregulated Glut-4, HK2 and CS, but downregulated PDK4 mRNA expression in MI+NRG-1 group compared with MI group (all P<0.01). Western blot assay showed significantly higher protein expression of NRG-1, p-ErbB4, Glut-4, HK2, PDH, CS in MI+NRG-1 group than in MI group (all P<0.01). Conclusion: NRG-1 could improve glucose uptake and utilization in myocardium by activating phosphorylation of myocardial ErbB4 receptor in MI rats, thus providing a therapeutic option for improving energy metabolism after MI.

Prognostic Impact of Fasting Plasma Glucose on Mortality and Re-Hospitalization in Patients with Acute Heart Failure / 中华医学杂志(英文版)

Background@#The impact of fasting plasma glucose (FPG) on survival outcomes in patients with acute heart failure (HF) is unclear, and the relationship between intensity of glycemic control of FPG in diabetes mellitus (DM) patients and HF prognosis remains uncertain. This retrospective study aimed to evaluate the prognostic impact of FPG in patients with acute HF.@*Methods@#A total of 624 patients hospitalized with acute HF from October 2000 to April 2014 were enrolled in this study. All patients were stratified by three groups according to their admission FPG levels (i.e., DM, impaired fasting glucose [IFG], and non-DM). All-cause and cardiovascular mortality was the primary end point, and HF re-hospitalization was the secondary end point during follow-up period.@*Results@#A total of 587 patients were included in final analysis. The all-cause mortality rates of patients with DM, IFG, and non-DM were 55.5%, 40.3%, and 39.2%, with significant difference (P = 0.001). Moreover, compared with those with IFG (34.3%) and non-DM (32.6%), patients with DM had significantly higher rate of cardiovascular mortality (45.1%). Multiple Cox regression analysis showed that DM as well as IFG was related to all-cause mortality (DM: hazard ratio [HR] = 1.936, P < 0.001; IFG: HR = 1.672, P = 0.019) and cardiovascular mortality (DM: HR = 1.739, P < 0.001; IFG: HR = 1.817, P = 0.013). However, they were both unrelated to HF re-hospitalization. DM patients with strictly controlled blood glucose (FPG <3.9 mmol/L) had higher all-cause mortality than patients with non-DM, IFG, and DM patients with moderately controlled glucose (3.9 mmol/L≤ FPG <7.0 mmol/L). Likewise, both the primary end point and secondary end point were found to be worse in DM patients with poorly controlled blood glucose (FPG ≥7.0 mmol/L).@*Conclusions@#IFG and DM were associated with higher all-cause mortality and cardiovascular mortality in patients with acute HF. The association between mortality and admission FPG in DM patients with acute HF appeared U-shaped.

IL-33 promotes IL-10 production in macrophages: a role for IL-33 in macrophage foam cell formation

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.

Role of Circulating Fibrocytes in Cardiac Fibrosis / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>It 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.</p><p><b>DATA SOURCES</b>This review is based on the data from 1994 to present obtained from PubMed. The search terms were "circulating fibrocytes " and "cardiac fibrosis ".</p><p><b>STUDY SELECTION</b>Articles and critical reviews, which are related to circulating fibrocytes and cardiac fibrosis, were selected.</p><p><b>RESULTS</b>Circulating 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.</p><p><b>CONCLUSIONS</b>Circulating fibrocytes are effector cells in cardiac fibrosis.</p>

Effect of Metabolic Syndrome on Risk Stratification for Left Atrial or Left Atrial Appendage Thrombus Formation in Patients with Nonvalvular Atrial Fibrillation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Metabolic syndrome (MS) is a risk factor for stroke and thromboembolism event. Left atrial or LA appendage (LA/LAA) thrombus is a surrogate of potential stroke. The relationship between MS and atrial thrombus remains unclear. In this study, we sought to investigate the effect of MS on risk stratification of LA/LAA thrombus formation in patients with nonvalvular atrial fibrillation (NVAF).</p><p><b>METHODS</b>This cross-sectional study enrolled 294 consecutive NVAF patients without prior anticoagulant and lipid-lowering therapies. LA/LAA thrombus was determined by transesophageal echocardiography. Risk assessment of LA/LAA thrombus was performed using the CHADS2 , CHA2DS2 -VASc, MS, CHADS2 -MS, and CHA2DS2 -VASc-MS scores. Logistic regression analyses were performed to determine which factors were significantly related to LA/LAA thrombus. Odds ratio (OR) including 95% confidence interval was also calculated. The predictive powers of different scores for the risk of LA/LAA thrombus were represented by C-statistics and compared by receiver operating characteristic (ROC) analysis.</p><p><b>RESULTS</b>LA/LAA thrombi were identified in 56 patients (19.0%). Logistic analysis showed that MS was the strongest risk factor for LA/LAA thrombus in NVAF patients (OR = 14.698, P < 0.001). ROC curve analyses revealed that the C-statistics of CHADS2 -MS and CHA2DS2 -VASc-MS was significantly higher than those of CHADS2 and CHA2DS2 -VASc scores (CHADS2 -MS vs. CHADS2 , 0.807 vs. 0.726, P = 0.0019). Furthermore, MS was helpful for identifying individuals with a high risk of LA/LAA thrombus in the population with a low risk of stroke (CHADS2 or CHA2DS2 -VASc score = 0).</p><p><b>CONCLUSIONS</b>MS is associated with LA/LAA thrombus risk in patients with NVAF. In addition to the CHADS2 and CHA2DS2 -VASc scores, the CHADS2 -MS and CHA2DS2 -VASc-MS scores provide additional information on stroke risk assessment.</p>

Carbon Monoxide Releasing Molecule Accelerates Reendothelialization after Carotid Artery Balloon Injury in Rat / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>This study was aimed to investigate the effects of carbon monoxide releasing molecule (CORM-2), a novel carbon monoxide carrier, on the reendothelialization of carotid artery in rat endothelial denudation model.</p><p><b>METHODS</b>Male rats subjected to carotid artery balloon injury were treated with CORM-2, inactive CORM-2 (iCORM-2) or dimethyl sulfoxide (DMSO). The reendothelialization capacity was evaluated by Evans Blue dye and the immunostaining with anti-CD31 antibody. The number of circulating endothelial progenitor cells (EPCs) was detected by flow cytometry. The proliferation, migration, and adhesion of human umbilical vein endothelial cells (HUVECs) were assessed by using [3H]thymidine, Boyden chamber and human fibronectin respectively. The expressions of protein were detected by using western blot analysis.</p><p><b>RESULTS</b>CORM-2 remarkably accelerated the re-endothelialization 5 d later and inhibited neointima formation 28 d later. In addition, the number of peripheral EPCs significantly increased in CORM-2-treated rats than that in iCORM-2 or DMSO-treated rats after 5 d later. In vitro experiments, CORM-2 significantly enhanced the proliferation, migration and adhesion of HUVECs. The levels of Akt, eNOS phosphorylation, and NO generation in HUVECs were also much higher in CORM-2 treated group. Blocking of PI3K/Akt/eNOS signaling pathway markedly suppressed the enhanced migration and adhesion of HUVECs induced by CORM-2.</p><p><b>CONCLUSION</b>CORM-2 could promote endothelial repair, and inhibit neointima formation after carotid artery balloon injury, which might be associated with the function changes of HUVECs regulated by PI3K/Akt/eNOS pathway.</p>

Association of higher resistin levels with inflammatory activation and endothelial dysfunction in patients with essential hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Some studies have shown that serum resistin levels increase in hypertensive patients. Whether the increase of resistin is related to inflammatory or vascular endothelial function is still unknown. We investigated the relationship of increased resistin levels to inflammatory factors and circulating biomarkers of vascular endothelial function in hypertensive patients.</p><p><b>METHODS</b>One hundred and forty-four nondiabetic patients with new onset, hypertension were recruited. Blood pressure, blood glucose, insulin, resistin, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), von Willebrand factor (vWF), endothelin-1 (ET-1) and nitric oxide (NO) were measured. The homeostasis model assessment, insulin resistance index (HOMA-IR) was calculated. Patients were divided into two groups according to the median level of resistin. Cytokine levels and indicators of vascular endothelial function were compared. Multiple linear regression was used to determine factors influencing resistin.</p><p><b>RESULTS</b>Serum resistin ranged from 2.57 ng/ml to 20.18 ng/ml in hypertensive patients. High resistin group (> 8.36 ng/ml) had higher levels of TNF-α, IL-6, vWF and ET-1 but lower level of NO compared with low resistin group (P < 0.01). Resistin was positively correlated with body mass index, systolic blood pressure, HOMA-IR, low-density lipoprotein cholesterol, TNF-α and ET-1 but negatively correlated with NO (all P < 0.05). Multiple linear regression analysis revealed that HOMA-IR, TNF-α, NO and ET-1 are independent predictors of resistin with standardized regression coefficients of 0.625, 0.368, -0.260 and 0.222, respectively (all P < 0.01).</p><p><b>CONCLUSIONS</b>We conclude that higher resistin levels are associated with inflammatory activation and endothelial dysfunction, because patients with essential hypertension have increased TNF-α, IL-6, vWF and ET-1 and decreased NO. Moreover, the statistical association of resistin with TNF-α, NO and ET-1 suggests involvement of resistin in the progression of hypertension by influencing inflammation and endothelial function.</p>

Impact of insulin resistance on prognosis in non-diabetic patients with acute coronary syndromes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the impact of insulin resistance (IR) on prognosis in non-diabetic acute coronary syndrome patients.</p><p><b>METHODS</b>In 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.</p><p><b>RESULTS</b>Incidence 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.</p><p><b>CONCLUSIONS</b>Increased insulin resistance is linked with poor prognosis of non-diabetic patients with acute coronary syndrome.</p>

Biomarkers of endothelial dysfunction and risk of early organ damage: a comparison between patients with primary aldosteronism and essential hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare plasma concentrations of biomarkers of endothelial dysfunction between patients with primary aldosteronism (PA) and essential hypertension (EH), and to determine whether elevated levels of these biomarkers could predict development of early organ damage.</p><p><b>METHODS</b>Thirty-six PA patients and 39 EH patients matched for age, sex, blood pressure and duration of hypertension were included in this study. Plasma levels of biomarkers reflecting endothelial dysfunction (von Willebrand factor, vWF; soluble intercellular adhesion molecule 1, sICAM-1; and oxidized low density lipoprotein, ox-LDL) were detected and compared between PA and EH patients. Left ventricular mass index (LVMI) determined by echocardiography, 24-hour urinary protein quantitative determination and urinary albumin excretion rate (UAER) were analyzed to evaluate early organ damage. Left ventricular hypertrophy was defined as LVMI > 125 g/m(2) in men and > 120 g/m(2) in women, and UAER between 20 µg/min and 200 µg/min was defined as microalbuminuria.</p><p><b>RESULTS</b>vWF [(122.3 ± 53.8)% vs. (113.1 ± 68.3)%], sICAM-1 [(401.0 ± 74.1) µg/L vs. (300.9 ± 87.0) µg/L], ox-LDL [(13.6 ± 10.0) U/L vs. (8.1 ± 5.9) U/L], LVMI [(124.7 ± 33.6) g/m(2) vs. (109.1 ± 25.7) g/m(2)], 24-hour urinary protein quantitation [24 h UPQ, (0.17 ± 0.10) g vs. (0.09 ± 0.04) g] and UAER [(25.9 ± 7.7) µg/min vs. (9.7 ± 5.9) µg/min] were significantly higher in PA group than in EH group (all P < 0.05). Elevated plasma vWF, sICAM-1 levels and plasma aldosterone concentration independently predicted microalbuminuria. Whereas, elevated plasma vWF and ox-LDL levels, plasma aldosterone concentration and systolic blood pressure independently predicted left ventricular hypertrophy.</p><p><b>CONCLUSION</b>Patients with PA have severer endothelial dysfunction reflected by multiple biomarkers and earlier organ damage than patients with EH, and plasma aldosterone concentration and multiple endothelial dysfunction biomarkers could independently predict early organ damage.</p>

A prospective study to evaluate the efficacy of an intracardiac electrogram-based atrioventricular and interventricular intervals optimization method in cardiac resynchronization therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cardiac resynchronization therapy (CRT) with biventricular pacing improves cardiac function, functional capacity and quality of life in selected patients with heart failure. The current study aimed to evaluate the efficacy of the intracardiac electrogram (IEGM)-based optimization method, QuickOpt(TM), in Chinese patients treated with CRT.</p><p><b>METHODS</b>Aortic time velocity integrals (AVTI) achieved at the sensed atrioventricular (AV), paced AV and interventricular (VV) interval settings recommended by both QuickOpt(TM) and standard echocardiographic optimization were measured in 101 patients. Consistency and the strength of the relationship between the two timing cycle optimization methods were assessed by intra-class correlation coefficient (ICC).</p><p><b>RESULTS</b>The ICC showed good agreement and correlation with what the AVTI achieved at the optimal sensed AV (ICC = 0.9683 (0.9535 - 0.9785)), paced AV (ICC = 0.9642 (0.9475 - 0.9757)) and VV (ICC = 0.9730 (0.9602 - 0.9817)) interval settings determined by the two optimization methods. The average time required by echocardiographic optimization and by QuickOpt(TM) were (78.32 ± 32.40) minutes and (1.98 ± 1.64) minutes respectively (P < 0.0001).</p><p><b>CONCLUSION</b>The QuickOpt(TM) algorithm provides a quicker, simpler and reliable alternative to the standard method for timing cycle optimization.</p>

Surgical treatment of symptomatic Rathke's cleft cysts: clinical features, therapy considerations and outcomes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Rathke's cleft cyst (RCC) is one of the most common incidentally discovered sellar lesions, while symptomatic cases are relatively rare. Surgical treatment is recommended for symptomatic patients to drain the cyst content and to remove the capsule safely. The aim of this study was to clarify the clinical features, surgery considerations and therapy outcomes of symptomatic RCCs.</p><p><b>METHODS</b>Totally 42 patients (19 males and 23 females) were retrospectively reviewed with the diagnosis of RCCs under surgery resection at the Affiliated Hospital of Medical College, Qingdao University between January 2005 and December 2010.</p><p><b>RESULTS</b>Patients' age ranged from 6 to 67 years (mean of 41.6 years). The duration of symptoms ranged from 4 days to 10 years. Headache (69%), visual impairment (36%), and pituitary dysfunction (10%) were the most common presenting symptoms. The maximum diameter of cysts ranged from 6.0 to 46.7 mm (mean of 20.07 mm). Of the 42 patients, 36 underwent endonasal transsphenoidal approach and the others underwent transcranial approach. Thirty patients had a subtotal resection and decompression, while 12 patients had a total cyst resection. Cysts of 28 patients were lined by simple cubical or columnar epithelium, and cysts of 34 patients were filled by amorphous colloid material, that was the characteristic of RCCs. The majority of patients presented with a simple headache, and 93% of this group experienced a complete improvement after surgery. Twelve of 15 patients (80%) with preoperative visual deficits experienced an improvement in their vision after surgery. All of those patients with pituitary dysfunction experienced an improved endocrine status. The endocrinological complication usually was diabetes insipidus, and postoperative transient diabetes insipidus occurred in 13 (31%) patients without any permanent diabetes insipidus. The overall recurrence rate was 7% at a mean follow-up of 22 months (range 12 - 60 months).</p><p><b>CONCLUSIONS</b>Surgical treatment is to drain the contents of the cyst and to remove the capsule as much as possible under the precondition that does not increase the complications. Biopsy and decompression procedures are recommended for most cases.</p>

Increased expression of granulocyte colony-stimulating factor mediates mesenchymal stem cells recruitment after vascular injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent 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.</p><p><b>METHODS</b>Balloon-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.</p><p><b>RESULTS</b>Morphometric 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.</p><p><b>CONCLUSION</b>Increased 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.</p>

Diagnostic value of 64-slice spiral computed tomography coronary angiography for coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To assess the diagnostic accuracy of 64-slice computed tomography coronary angiography (64-SCTCA) in individuals with suspected coronary artery disease (CAD).</p><p><b>METHODS</b>The study enrolled 285 individuals undergoing 64-SCTCA with calcium scoring and thereafter invasive coronary angiography (CAG) within 4 weeks for suspected CAD. Pretest probability of having obstructive CAD was determined using the Duke clinical score, which was estimated by type of chest discomfort, age, gender, and traditional risk factors and stratified into 3 levels of probability: low (≤ 30%, n = 80), intermediate (31% to 70%, n = 92), and high (≥ 71%, n = 113). CAD was defined as the presence of at least one vessel of ≥ 50% coronary stenosis on CAG.</p><p><b>RESULTS</b>The patient-based diagnostic accuracy of 64-SCTCA for detecting CAD according to CAG revealed a sensitivity of 81.2%, a specificity of 93.3%, a positive predictive value of 68.0% and negative predictive value of 96.6%. The CAD prevalence in the low, intermediate and high risk groups according to Duke probability was 46.3%, 72.8% and 82.3%, respectively. The sensitivity and positive predictive value were lower in the low probability group than those in the intermediate and high probability groups. For those with coronary artery Agatston calcium score > 400, the diagnostic accuracy was linked with a higher sensitivity but lower specificity. The diagnostic value of 64-SCTCA for proximal and mid-segment of coronary artery was superior to that for distal segment.</p><p><b>CONCLUSIONS</b>64-SCTCA is mainly indicated in individuals with an intermediate probability of having CAD. The diagnostic value of 64-SCTCA could be affected by coronary artery calcium, lesion location and vessel diameter.</p>

Impact of mean fasting glucose over the first 72 hours on in-hospital outcomes of patients with ST-segment elevation myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the impact of mean fasting glucose over the first 72 hours after admission on in-hospital outcomes in patients with ST-segment elevation myocardial infarction (STEMI).</p><p><b>METHODS</b>The data of 357 non-diabetic patients hospitalized with STEMI were collected from the database of Sun Yat-sen Memorial Hospital, affiliated to Sun Yat-sen University between January 2006 and April 2009. The patients were categorized into 3 groups according to mean fasting glucose over the first 72 hours after admission: < 5.6 (n = 165), 5.6 - 7.0 (n = 122) and > 7.0 mmol/L (n = 70). Clinical characteristics, therapeutic approaches and the incidence of heart failure, malignant arrhythmias, and death during hospitalization were compared among groups. Multivariate logistic regression analysis was performed to determine the association between risk factors and in-hospital outcomes. Receiver-operator characteristic (ROC) curve was generated to assess the power of mean fasting glucose on predicting in-hospital death.</p><p><b>RESULTS</b>Age, past history of infarction and early revascularization therapy were similar among groups. Heart rate on admission, white blood cell count, peak CK-MB level, and proportion of extensive anterior infarction were increased in proportion to higher mean fasting glucose levels. Higher mean fasting glucose levels were associated with increased risk of reduced left ventricular ejection fraction, heart failure characterized by higher Killip class, and malignant arrhythmias. After multivariate adjustment, mean fasting glucose remained to be an independent risk factor for increased in-hospital death of patients with STEMI (OR = 1.31, 95%CI: 1.10 - 1.57; P = 0.003). Mean fasting glucose had the higher area under the ROC curve than admission glucose or fasting glucose after admission based on single measurement (0.758, 0.674 and 0.717; P < 0.001).</p><p><b>CONCLUSION</b>Mean fasting glucose during first 72 hours after admission is an independent predictor for in-hospital death and complications in patients with STEMI, which is superior to admission glucose or fasting glucose after admission based on single measurement in predicting in-hospital outcomes.</p>

Alcohol consumption and coronary heart disease in Eastern Asian men: a meta-analysis of prospective cohort studies / 中华心血管病杂志

<p><b>OBJECTIVE</b>To assess the dose-response relationship between alcohol consumption and relative risk of coronary heart disease (CHD) morbidity, mortality and all-cause mortality among Eastern Asian men.</p><p><b>METHODS</b>Potential prospective cohort studies were retrieved by searching Pubmed (1966 - 2000), Biosis Previews (1980 - 2009), Embase (1980 - 2009) and ISI Web of Knowledge (1986 - 2009) using Medical Subject Headings alcohol drinking, ethanol, coronary heart (or artery) disease, myocardial infarction, mortality, etc; and Koreans, or Japanese or Chinese. From the 28 relevant retrieved reports, 15 prospective cohort studies met the criteria were included. Information on study design, participant characteristics, level of alcohol consumption, CHD outcome, control for potential confounding factors, and risk estimates were abstracted using a standardized protocol. For each study, relative risks (RR) and 95% confidence intervals (CI) were extracted and pooled with either a fixed effect model or random effect model according to the result of the test of heterogeneity.</p><p><b>RESULTS</b>Due to the limited available data for women, this study only comprised of 2406 cases of CHD among 177 723 male subjects. Findings were also pooled from 216 233 male subjects and 15 462 deaths from any cause. Compared with nondrinkers, the RRs on CHD morbidity for those who drank alcohol ≤ 20, 21 - 40, 41 - 60, > 60 g/d were 0.65 (0.34 - 1.23, P = 0.18), 0.48 (0.26 - 0.87, P = 0.02), 0.46 (0.32 - 0.67, P < 0.01), and 0.48 (0.29 - 0.78, P < 0.01) respectively; the RRs on CHD mortality were 0.98 (0.73 - 1.31, P = 0.87), 0.68 (0.58 - 0.79, P < 0.01), 0.64 (0.43 - 0.96, P = 0.03), 0.75 (0.54 - 1.03, P = 0.08); and on all-cause mortality were 0.83 (0.79 - 0.91, P < 0.01), 0.93 (0.87 - 0.99, P = 0.03), 1.01 (0.95 - 1.07, P = 0.86), 1.32 (1.29 - 1.36, P < 0.01).</p><p><b>CONCLUSION</b>Light-to-moderate alcohol intake was associated with decreased risk of CHD morbidity and mortality, while heavy alcohol intake was associated with increased all-cause mortality among Eastern Asian men.</p>

Potential proarrhythmic effect of cardiac resynchronization therapy during perioperative period: data from a single cardiac center / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cardiac resynchronization therapy (CRT) could improve heart function, symptom status, quality of life and reduce hospitalization and mortality in patients with severe heart failure (HF) with optimal medical management. However, the possible adverse effects of CRT are often ignored by clinicians.</p><p><b>METHOD</b>A retrospective analysis of CRT over a 6-year period was made in a single cardiac center.</p><p><b>RESULTS</b>Fifty-four patients were treated with CRT(D) device, aged (57 ± 11) years, with left ventricular ejection fraction of (32.1 ± 9.8)%, of which 4 (7%) developed ventricular tachycardia/ventricular fibrillation (VT/VF) or junctional tachycardia after operation. Except for one with frequent ventricular premature beat before operation, the others had no previous history of ventricular arrhythmia. Of the 4 patients, 3 had dilated cardiomyopathy and 1 had ischemic cardiomyopathy, and tachycardia occurred within 3 days after operation. Sustained, refractory VT and subsequent VF occurred in one patient, frequent nonsustained VT in two patients and nonparoxysmal atrioventricular junctional tachycardia in one patient. VT was managed by amiodarone in two patients, amiodarone together with beta-blocker in one patient, and junctional tachycardia was terminated by overdrive pacing. During over 12-month follow-up, except for one patient's death due to refractory heart and respiratory failure in hospital, the others remain alive and arrhythmia-free.</p><p><b>CONCLUSIONS</b>New-onset VT/VF or junctional tachycardia may occur in a minority of patients with or without prior history of tachycardia after biventricular pacing. Arrhythmia can be managed by conventional therapy, but may require temporary discontinuation of pacing. More observational studies should be performed to determine the potential proarrhythmic effect of CRT.</p>

R25G mutation in exon 1 of LMNA gene is associated with dilated cardiomyopathy and limb-girdle muscular dystrophy 1B / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mutations 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.</p><p><b>METHODS</b>All 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.</p><p><b>RESULTS</b>Ten 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).</p><p><b>CONCLUSIONS</b>The 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.</p>

PPAR gamma agonist rosiglitazone alleviates hypoxia/reoxygenation-induced oxidative stress and apoptosis in rat cardiac myocytes / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effects of different concentrations of PPAR gamma agonist rosiglitazone on hypoxia/reoxygenation-induced oxidative stress, cell viability and apoptosis in rat cardiac myocytes.</p><p><b>METHODS</b>Cultured rat cardiac myocytes were divided into 5 groups, namely group I (normal group), group II (20 micromo/L ROS group), group III (I/R group), group IV (I/R+20 micromo/L ROS group), and group V (I/R+80 micromo/L ROS group). Group IV and group V were treated with rosiglitazone 12 h before hypoxia/reoxygenation. The changes in cell morphology were observed under optical and transmission electron microscopy, and levels of malondialdehyde (MDA), superoxide dismutase (SOD) activity, and lactate dehydrogenase (LDH) content were determined after the treatment. MTT assay was performed to assess the cell viability and flow cytometry was used to analyze the cell apoptosis.</p><p><b>RESULTS</b>Hypoxia/reoxygenation resulted in significantly increased MDA and LDH contents and apoptosis of the cardiac myocytes (P<0.05), but lowered SOD activity and the cell viability (P<0.05). The MDA and LDH contents and apoptotic rate were significantly lower but SOD content and cell vitality significantly higher in groups IV and V than in group III (P<0.05). Group V showed significantly lower MDA and LDH contents and apoptotic rate but higher but SOD content and cell vitality than group IV (P<0.05). Electron microscopy revealed obvious apoptotic changes in group III, and only mild changes were found in group V.</p><p><b>CONCLUSION</b>Rosiglitazone can significantly reduce hypoxia/reoxygenation-induced oxidative stress in cardiac myocytes, improve the cell viability and dose-dependently reduce the apoptotic rate of the cardiac myocytes.</p>

Blockades of angiotensin and aldosterone reduce osteopontin expression and interstitial fibrosis infiltration in rats with myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been reported that osteopontin has an important role in cardiac fibrosis and remodeling. However, its direct mechanisms remain unclear. The purpose of this study was to investigate the role of angiotensin and aldosterone blockades in cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted (MI) rats.</p><p><b>METHODS</b>Fifty SD rats that survived 24 hours after ligating left anterior descending coronary artery were randomly divided into three groups: MI-saline group (n = 15, 5 ml/d), MI-perindopril group (n = 18, perindopril 2 mgxkg(-1)d(-1)) and MI-spironolacton (n = 17, spironolacton 20 mgxkg(-1)xd(-1)). A sham operation group (n = 15) was selected as non-infarcted control. At 6 weeks after treatment, hemodynamic pararmeters and left ventricular function were measured with catheterization, interstitial fibrosis infiltration and cardiomyocyte diameters were evaluated histologically. Myocardium osteopontin protein expression level in the non-infarcted myocardium was detected by Western blotting.</p><p><b>RESULTS</b>No osteopontin protein was detected in the myocardium of sham-operation rats. High levels of osteopontin protein expression were detected in the MI-saline rats, but the levels were suppressed in the MI-perindopril and MI-spironolacton rats at 6 weeks following MI (P < 0.01, respectively). Compared with the sham operation group, all rats in the MI group showed marked interstitial fibrosis infiltration in the non-infarction area, higher ventricular weight/body weight ratio, significantly increased cardiomyocyte diameter (P < 0.01, respectively), and developed significant systolic and diastolic dysfunction as indicated by decreased left ventricular systolic pressure (LVSP) and +/-dp/dt, as well as increased left ventricular end-diastolic pressure (LVEDP) (P < 0.01, respectively). Angiotensin and aldosterone blockades partly prevented cardiac fibrosis and systolic and diastolic dysfunction (P < 0.01, respectively).</p><p><b>CONCLUSION</b>Treatment with angiotensin and aldosterone blockades inhibits expression of osteopontin in the non-infarcted myocardium and prevents cardiac remodeling following MI.</p>

Effect of AP-1 decoy oligodeoxynucleotides on neonatal rat cardiac fibroblast proliferation and collagen synthesis / 南方医科大学学报

<p><b>OBJECTIVE</b>To 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).</p><p><b>METHODS</b>The 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).</p><p><b>RESULTS</b>With 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).</p><p><b>CONCLUSION</b>AP-1 decoy can inhibit AngII-induced rat CF proliferation and collagen synthesis possibly by affecting the cell cycle distribution.</p>