Progress of STIM1, a dynamic calcium signal transducer, in cardiovascular diseases / 中国病理生理杂志

Stromal interaction molecule 1 (STIM1) is a transmembrane protein of the endoplasmic reticulum (ER) , a Ca2+ transducer in ER that activates the store-operated calcium channel.Through Orai1 protein, STIM1 adjusts the intracellular and extracellular calcium concentration.This way is called a store-operated Ca2+ entry.STIM1 plays a key role in phenotypic transformation of vascular smooth muscle cells, proliferation of endothelial cells, myocardial hypertrophy and myocardial fibrosis to regulate lots of cardiovascular diseases, such as atherosclerosis, congestive heart failure and systemic hypertension.STIM1 is closely related to cardiovascular diseases through calcium signal.The research progress of STIM1 in cardiovascular diseases is mainly discussed in this article.

Relationship Between Serum Bilirubin Level and the Severity of Coronary Artery Disease / 中国循环杂志

Objective: To explore the relationship between serum bilirubin level and the severity of coronary artery disease (CAD). Methods: A total of 568 patients treated in our hospital from 2014-07 to 2016-03 were studied. Based on coronary angiography (CAG), the patients were divided into 2 groups: CAD group, n=438 and Non-CAD group, n=130. CAD group had 166 patients with single vessel disease, 150 with double vessel disease and 122 with triple vessel disease; taking Gensini score 34 as the border, there were 219 patients with low Gensini score and 219 with high Gensini score. Taking total bilirubin (TBIL) level>17.1 μmol/L as the border, the patients were divided into another set of 2 groups: Normal TBIL group, n=426 and High TBIL group, n=142. Clinical data, biochemical parameters, blood routine examination, color doppler ultrasound and CAG results were recorded. Blood levels of TBIL, direct bilirubin (DBIL) and indirect bilirubin (IBIL) were compared among different groups. Results: ①Compared with Non-CAD group, CAD group had decreased serum levels of TBIL, DBIL and IBIL, P<0.05, the detective rate of hyperbilirubinemia had decreasing trend; while detective rate of CAD was similar between Normal TBIL group and High TBIL group, P>0.05. ②In CAD group, the patients with more coronary branch lesions and the higher Gensini scores had the lower serum levels of TBIL, DBIL and IBIL, P<0.05. Pearson correlation analysis showed that TBIL, DBIL and IBIL were positively related to LVEF (r=0.390, r=0.283 and r=0.426), all P<0.05. ③Multi-linear regression analysis indicated that DBIL, IBIL level was the independent risk factor for CAD occurrence and having negative correlation to CAD (B=-3.766, B=-2.705), both P<0.05. ④TBIL, DBIL and IBIL levels were negatively related to hs-CRP in CAD patients (r=-0.617, r=-0.473 and r=-0.580),allP<0.05. Conclusion: Serum bilirubin level was negatively correlated to the degree of the cornary stenosis, which is independent of its forms, low bilirubin might be an independent risk factor of CAD occurrence.

Sanguinarine Attenuates Lipopolysaccharide-induced Inflammation and Apoptosis by Inhibiting the TLR4/NF-κB Pathway in H9c2 Cardiomyocytes / 华中科技大学学报（医学）（英德文版）

The inflammatory response is involved in the pathogenesis of the most common types of heart disease.Sanguinarine (SAN) has various pharmacological properties such as anti-inflammatory,antioxidant,antibacterial,antitumor,and immune-enhancing properties.However,few studies have investigated the effects of SAN on lipopolysaccharide (LPS)-induced inflammatory and apoptotic responses in H9c2 cardiomyocytes.Therefore,in this study,H9c2 cells were co-treated with SAN and LPS,and the mRNA levels of pro-inflammation markers and the apoptosis rate were measured to clarify the effect of SAN on cardiac inflammation.The underlying mechanism was further investigated by detecting the activation of Toll-like receptor (TLR)4/nuclear factor-κB (NF-κB) signaling pathways.As a result,increased mRNA expression of interleukin (IL)-1 β,IL-6,and TNFα induced by LPS was attenuated after SAN treatment;LPS-induced apoptosis of H9c2 cardiomyocytes and cleaved-caspase 8,9,3 were all significantly reduced by SAN.Further experiments showed that the beneficial effect of SAN on blocking the inflammation and apoptosis of H9c2 cardiomyocytes induced by LPS was associated with suppression of the TLR4/NF-κB signaling pathway.It was suggested that SAN suppressed the LPS-induced inflammation and apoptosis of H9c2 cardiomyocytes,which may be mediated by inhibition of the TLR4/NF-κB signaling pathway.Thus,SAN may be a feasible therapy to treat sepsis patients with cardiac dysfunction.

Sanguinarine Attenuates Lipopolysaccharide-induced Inflammation and Apoptosis by Inhibiting the TLR4/NF-κB Pathway in H9c2 Cardiomyocytes / 华中科技大学学报（医学）（英德文版）

The inflammatory response is involved in the pathogenesis of the most common types of heart disease.Sanguinarine (SAN) has various pharmacological properties such as anti-inflammatory,antioxidant,antibacterial,antitumor,and immune-enhancing properties.However,few studies have investigated the effects of SAN on lipopolysaccharide (LPS)-induced inflammatory and apoptotic responses in H9c2 cardiomyocytes.Therefore,in this study,H9c2 cells were co-treated with SAN and LPS,and the mRNA levels of pro-inflammation markers and the apoptosis rate were measured to clarify the effect of SAN on cardiac inflammation.The underlying mechanism was further investigated by detecting the activation of Toll-like receptor (TLR)4/nuclear factor-κB (NF-κB) signaling pathways.As a result,increased mRNA expression of interleukin (IL)-1 β,IL-6,and TNFα induced by LPS was attenuated after SAN treatment;LPS-induced apoptosis of H9c2 cardiomyocytes and cleaved-caspase 8,9,3 were all significantly reduced by SAN.Further experiments showed that the beneficial effect of SAN on blocking the inflammation and apoptosis of H9c2 cardiomyocytes induced by LPS was associated with suppression of the TLR4/NF-κB signaling pathway.It was suggested that SAN suppressed the LPS-induced inflammation and apoptosis of H9c2 cardiomyocytes,which may be mediated by inhibition of the TLR4/NF-κB signaling pathway.Thus,SAN may be a feasible therapy to treat sepsis patients with cardiac dysfunction.

Effects of stem cell therapy on dilated cardiomyopathy

To perform a meta-analysis of clinical trials and investigate the effect of stem cell therapy on dilated cardiomyopathy. A systematic literature search was carried out between May 2012 and July 2013 in PubMed, Medline, Cochrane Library, and Excerpta Medica Database [EMBASE]. The study took place in the Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China. The weighted mean difference [WMD] was calculated for left ventricular ejection fraction [LVEF], left ventricular end-diastolic diameter [LVEDD], mortality and heart transplantation, and the 6-minute walk test [6-MWT] distance using the RevMan 5.0 software. Seven trials with 599 participants evaluated the association between the stem cell therapy and control groups. Compared with the control group, stem cell therapy group improved the LVEF [WMD: 3.98%, 95% confidence interval [CI]: 0.55 - 7.41%, p=0.02] and the 6-MWT distance [WMD: 132.12 m, 95% CI: 88.15-176.09 m, p<0.00001], and reduced mortality and heart transplantation [odds ratio [OR]: 0.48, 95% CI: 0.29-0.80, p=0.005]. However, the LVEDD showed no significant difference between the 2 groups [WMD: -1.53 mm, 95% CI: -1.15-0.10 mm, p=0.10]. This meta-analysis demonstrated that stem cell therapy improves cardiac function and reduces mortality in dilated cardiomyopathy patients, which suggested that stem cell therapy may represent a new therapy option for dilated cardiomyopathy.

Effect of temperature on hospital admission among patients with chronic systolic heart failure / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the effect of temperature on hospital admission among patients with chronic systolic heart failure (CSHF).</p><p><b>METHODS</b>Data regarding in-hospital patients with CSHF were gathered from 12 hospitals in Hubei province, between 2000 and 2010. Patients with a history of congenital heart disease and the history of cancer from this series, were excluded. Chi-square (χ(2)) tests and t tests were used for descriptive analysis. Univariate and multivariate logistic regression methods were performed to determinate the risk of hospital admission of every month to compare with the previous one. We used 2-tailed 95% confidence interval (CI), and tests with P < 0.01 to consider the significant levels, statistically. We also used the SPSS 13.0 for Windows, release 15, 2006 (SPSS Inc, Chicago, Ill) for data analyses.</p><p><b>RESULTS</b>(1) 48 964 patients were enrolled in the present study. The numbers of admission increased 18.71%, 13.84%, -21.90%, -34.62%, -21.97%, -3.81%, -2.04%, 10.13%, -17.13%, -0.85%, 21.54% and 42.70% from January to December when compared to the average number of admission. (2) The odds ratios (ORs) (95% CI, P values) of hospital admission in January, February and December were 1.09 (0.96 - 1.23, 0.54), 0.98 (0.84 - 1.10, 0.46) and 0.96 (0.84 - 1.08, 0.59), respectively in females which did not show any significant differences when compared to the number in August. However the ratios were 0.61 (0.54 - 0.69, < 0.01), 0.80 (0.68 - 0.92, < 0.01) and 0.73 (0.64 - 0.83, < 0.01), respectively, in males that showed significant differences when, compared to the figures in August. (3) The OR of admission increased more when temperature got lower for patients with coronary artery disease, hypertension heart disease or rheumatic heart disease, but not with dilated cardiomyopathy. (4) The OR of admission showed a different impact on patients with different occupation, along with the change of temperature. Low or high temperature did not seem to have different effects on the OR of admission in patients who were free-lanced or unemployed.</p><p><b>CONCLUSION</b>Temperature seemed to have significant effects on the risk of admission, which related to gender, etiology or occupation.</p>

Prognostic value of late gadolinium enhancement in dilated cardiomyopathy patients. A meta-analysis

To evaluate the prognostic value of late gadolinium enhancement [LGE] in dilated cardiomyopathy [DCM] patients. We searched PubMed, MEDLINE, the Cochrane library and EMBASE databases from September to December 2012 in the Renmin Hospital of Wuhan University, Wuhan, China for studies of LGE in DCM patients. We extracted the clinical outcomes [all-cause mortality, cardiovascular mortality, sudden cardiac death [SCD], aborted SCD, heart failure hospitalization] after carefully reviewed. A meta-analysis was performed to calculate pooled odds ratios [OR] with 95% confidence intervals [CIs] for prognostic outcomes in LGE positive versus LGE negative patients with DCM. Five studies for 545 DCM patients were contained in this meta-analysis. The results showed LGE positive patients was significantly associated with higher cardiovascular mortality [pooled OR: 2.67; 95% CI: 1.12-6.35; p=0.03], aborted SCD [pooled OR: 5.26; 95% CI: 1.57-17.55; p=0.007], and heart failure hospitalization [pooled OR: 3.91; 95% CI: 1.99-7.69; p<0.001]. Late gadolinium enhancement during cardiac MRI is significantly associated with cardiovascular mortality, aborted SCD and heart failure hospitalization in DCM patients. The LGE can be a potential stratification tool to predict the risk of cardiac events among patients with DCM

Comparison of the Effects of Propofol and Midazolam on Inflammation and Oxidase Stress in Children with Congenital Heart Disease Undergoing Cardiac Surgery

PURPOSE: To investigate and compare the effects of propofol and midazolam on inflammation and oxidase stress in children with congenital heart disease undergoing cardiac surgery. MATERIALS AND METHODS: Thirty-two ASA class I-II children with congenital heart disease undergoing cardiac surgery were randomly divided into two groups: propofol combined with low dose fentanyl (PF group, n = 16) and midazolam combined with low dose fentanyl (MF group, n = 16). Tracheal extubation time and length of Intensive Care Unit (ICU) stay were recorded. Blood samples were taken before operation (T0), at 2 h after release of the aorta cross-clamp (T3) and at 24 h after operation (T4) to measure interleukin 6 (IL-6), IL-8, superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Myocardium samples were collected at 10-20 min after aorta cross-clamp (T1) and at 10-20 min after the release of the aorta cross-clamp (T2) to detect heme oxygenase-1 (HO-1) expression. RESULTS: Tracheal extubation time and length of ICU stay in PF group were significantly shorter than those of the MF group (p < 0.05, respectively). After cardiopulmonary bypass, IL-6, IL-8 and MDA levels were significantly increased, and the SOD level was significantly reduced in both two groups, but PF group exhibited lower IL-6, IL-8 and MDA levels and higher SOD levels than the MF group (p < 0.05, respectively). The HO-1 expression in the PF group was significantly higher than that in MF group at the corresponding time points (p < 0.05, respectively). CONCLUSION: Propofol is superior to midazolam in reducing inflammation and oxidase stress and in improving post-operation recovery in children with congenital heart disease undergoing cardiac surgery.

Effects of BmKIM on sodium current of isolated cardiomyocytes, transmembrane action potential and aconitine induced arrhythmia in vivo in rabbits / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of recombinant BmKIM (poly-peptide derived from Asian Scorpion Buthus martensi Karsch) on the sodium current (I(Na)) of isolated ventricular myocytes, transmembrane action potential and aconitine induced arrhythmia in vivo in rabbits.</p><p><b>METHODS</b>Ventricular myocytes were enzymatically dissociated from adult rabbits. Whole-cell patch-clamp technique was used to record voltage-dependent I(Na). Standard transmembrane action potentials in rabbit hearts in vivo were recorded by using floating glass microelectrodes. Incidence of arrhythmias, the early after depolarization (EAD) and/or delay after depolarization (DAD) were measured in vivo in rabbits post aconitine (100 microg/kg, iv) in the absence or presence of BmKIM (50 microg/kg iv).</p><p><b>RESULTS</b>(1) BmKIM significantly inhibited I(Na) in a voltage-dependent manner and significantly shifted the I-V curves of I(Na) upward. BmKIM left shifted the inactivation curve of I(Na) and voltages at 50% inactivation of I(Na) were changed from (-70.8 +/- 2.6) mV to (-84.8 +/- 3.5) mV (P < 0.05). BmKIM prolonged the recovery of inactivation of I(Na). In the presence of BmKIM, the time constants of recovery (both tau(f) and tau(s)) of I(Na) were significantly prolonged from (28.9 +/- 6.1) ms and (107 +/- 21.6) ms in control group to (54.2 +/- 7.9) ms (P < 0.05) and (211.1 +/- 34.6) ms (P < 0.01), respectively. (2) BmKIM significantly shortened 50% and 90% of action potential duration (APD(50) and APD(90)), and reduced action potential amplitude (APA), declined maximum up stroke velocity of action potential (V(max)) in vivo. The Q-T duration was shortened and heart rate significantly increased post BmKIM injection. (3) Incidence of aconitine induced ventricular arrhythmias (77.8%) was significantly reduced by BmKIM (22.2%, P < 0.01).</p><p><b>CONCLUSIONS</b>BmKIM significantly blocked I(Na) through affecting the inactivated state of I(Na) in rabbit ventricular myocytes. BmKIM could attenuate the influx of I(Na), therefore shorten action potential duration and reduce action potential amplitude and reduce the incidence of aconitine induced arrhythmias.</p>

Interventricular septum motion abnormalities: unexpected echocardiographic changes of Brugada syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There remains controversy about whether Brugada syndrome (BS) has structural heart changes. We occasionally noted that a patient with BS had a quite unusual regional wall motion abnormality at the basal segment of the interventricular septum (IVS) during echocardiographic examination. The unexpected finding promoted us to reexamine our patients with BS by echocardiographic interrogation in the present study.</p><p><b>METHODS</b>Patients with BS (n = 11), patients with complete right bundle branch block (RBBB) (n = 11), and control subjects (n = 11) were enrolled in this study. Two-dimensional echocardiography (2DE) was performed to obtain parasternal left ventricular long axis view on which M-mode scanning line was adjusted to be perpendicular to the basal segment of IVS for delineation of the segmental motion curve, with a simultaneously electrocardiographic tracing.</p><p><b>RESULTS</b>2DE revealed a rapid swing motion shifting toward the right ventricle of the IVS basal segment at early systole in 73% (8/11) patients with BS, which was further confirmed on the M-mode curve evidenced by an early systolic notch toward the right ventricle. The position of the notch corresponded to C-point on the mitral motion curve, lasting for (53 +/- 5) ms. There were no similar changes both in patients with RBBB and in the control subjects.</p><p><b>CONCLUSION</b>IVS basal motion abnormalities at early-systolic phase may be the novel finding of BS.</p>

The role of isoprenaline-induced, calcium-activated transient outward chloride current in atrial electrical remodeling of rabbit / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the changes of the L-type calcium current (I(Ca, L)) and the calcium-activated transient outward chloride current (I(Cl, Ca)), and the repolarization characteristic of action potential in phase 1 under isoprenaline (ISO) stimulation in atrium myocytes of rabbit.</p><p><b>METHODS</b>Atrium myocytes were obtained by enzymatic dissociation from a section of atrial free wall. The membrane currents and action potential were recorded by the whole-cell patch-clamp technique.</p><p><b>RESULTS</b>After recording I(Ca, L), atrium myocytes were perfused with ISO (1 micromol/L) immediately. Five minutes later, a transient outward current (I(to)) was significantly induced, and the peak of I(to) was gradually increased while I(Ca, L) gradually decreased with increasing in clamp voltage. The I(to) was resistant to 4-AP (3 mmol/L) but sensitive to DIDS (150 micromol/L, Cl(-) channel blocker). This current was blocked by CdCl(2) (200 micromol/L, Ca(2+) channel blocker). The elicited rate of I(to) was 91.67% (P < 0.05). (2) The shape of AP was like an inverse triangle with no plateau in Phase 2 after ISO (1 micromol/L) perfusion. Moreover, compared to the parameters of control group, APD(50) and APD(90) were significantly shortened from (65.4 +/- 4.2) ms and (95.8 +/- 3.8) ms to (12.8 +/- 3.8) ms and (27.0 +/- 4.7) ms, and reduced to 80.46% and 71.87%, respectively (P < 0.01, n = 12). 4-AP (3 mmol/L) had on obvious effect on the shape of AP, however, the plateau of AP in phase 2 was recovered by DIDS (150 micromol/L) perfusion, APD(50) and APD(90) were (41.1 +/- 4.5) ms and (79.6 +/- 3.4) ms respectively. Compared to the parameters of control group, there were no significant differences (P > 0.05, n = 12). These results indicated that ionic transport were changed by ISO perfusion in atrium myocytes and I(to) played an important role in the phase 1 repolarization of AP.</p><p><b>CONCLUSIONS</b>Before ISO administration, we could only observe I(Ca, L) in atrium myocytes of rabbit. After isoproterenol intervention, certain intracellular ionic consistency and membrane ionic channels were changed. Calcium activated chloride channel and I(to2) revealed obvious predominance which shorten APD significantly. Action potential showed a triangle with no plateau, suggesting an electrical remodeling in atrium myocytes. The remodeling of ionic channel is related possibly with the opening of Ca(2+)-activated Cl(-) current, which maybe the electrophysiological base of reentrant atrial tachycardia.</p>