Search

OBJECTIVE To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable. [ABSTRACT FROM AUTHOR]

Background The correlation among the ratios of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C), total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) and thin-cap fibroatheroma has not yet been established. Methods It was a single center, retrospective observational study. In total, we recruited 421 patients (82.4% men; mean age 65.73 ± 10.44 years) with one culprit vessel which determined by intravascular optical coherence tomography (OCT). The thinnest-capped fibroatheroma (TCFA) group was defined as lipid contents in > 2 quadrants, with the thinnest fibrous cap measuring less than 65 µm. Univariate and multivariate logistic regression were carried out to explore the relationship between lipoprotein ratios, TCFA and other characteristics of plaque. To compare different ratios, the area under curve (AUC) of receiver-operating characteristic (ROC) curve was assessed. Results OCT was performed in 421 patients (TCFA group (n = 109), non-TCFA group (n = 312)). LDL-C/HDL-C in the TCFA group was significantly higher than in the non-TCFA group (2.95 ± 1.20 vs. 2.43 ± 0.92, P < 0.05), as was TC/LDL in TCFA and non-TCFA group (4.57 ± 1.58 vs. 4.04 ± 1.13, P < 0.05). Both LDL-C/HDL-C (OR: 1.002 (1.002-1.003), P < 0.05) and TC/HDL-C (OR: 1.001 (1.001-1.004), P < 0.05) were considered independent factors for the prediction of TCFA according to the logistic regression. Based on the AUC comparison, LDL-C/HDL-C and TC/HDL-C had no significant difference statistically (LDL-C/HDL-C AUC: 0.63; TC/HDL-C AUC: 0.61; P = 0.10) for the prediction of TCFA. Conclusions LDL-C/HDL-C and TC/HDL-C could be the independent factors for predicting the presence of TCFA, indicating coronary plaque vulnerability in CAD patients. Moreover, TC/HDL-C also showed a comparative performance for the prediction of TCFA as LDL-C/HDL-C. [ABSTRACT FROM AUTHOR]

Objective To investigate whether ABO blood groups is associated with the severity of coronary artery disease (CAD). Methods Between January 2015 and December 2017, 1425 first diagnosed CAD patients confirmed by selective coronary angiography were recruited into this cross-sectional study, and their baseline characteristics, ABO blood groups, Gensini score were collected. Multiple linear regression analysis was performed to test the association between the severity of CAD and ABO blood groups. Results The Gensini score was significantly higher in the blood group A than in the non-A groups (41.2 ± 32 vs. 38 ± 27; P = 0.026). After adjusting for age, male, smoking, family history of CAD, hypertension, diabetes mellitus and hypercholesterolemia, multivariate linear regression indicated that blood group A was associated with the severity of CAD (β = 3.298, 95% CI: 0.91-6.505, P = 0.044). In diabetes group, A blood type was also associated with increased Gensini score (P = 0.02) after adjusting for age, male, family history of CAD, hypercholesterolemia, smoking and hypertension. Conclusion In this cross-sectional study, the data indicated that blood group A was an independent risk factor of severity of CAD in Chinese population and Chinese patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: T wave oversensing (TWOS) is a major drawback of implantable cardioverter defibrillator (ICD) and data on predictors of TWOS in ICD is limited.We aimed to calculate a novel index of T wave safety margin (TWSM) and assess its potential for evaluating TWOS during the procedure of ICD implantation. Methods and Results: Thirty-two consecutive patients with ICD implantation were enrolled. During each procedure of ICD implantation, different ICD generators were connected to implanted sensing lead through active-fixation leads and bridging cables. R and T wave amplitudes were measured on ICD printouts according to the gain. The ICDs were programed to the most sensitive settings to reveal possible TWOS. A novel index TWSM was calculated according to the corresponding sensing algorithm of ICD. There was discrepancy of R wave amplitudes measured by different ICDs (P<0.01). In Fortify and Teligen ICDs, T wave amplitudes showed no difference (P>0.05) and TWSMs were sufficiently high (post sensing: 13.0 ± 7.6 and 28.3 ± 16.5, respectively, post pacing: 5.0 ± 2.2 and 4.6 ± 0.9, respectively). In nine patients with 10 TWOS episodes detected during the procedure of ICD implantation, generators with the highest TWSM were chosen. Only one TWOS episode during pacing was recorded during the 25±7 mo follow-up period. Conclusions: We first propose the index of TWSM during ICD implantation as a potentially efficient predictor for TWOS. Evaluation of TWSM might help to reduce TWOS episodes in patients with high risk of TWOS. Prospective studies are warranted to validate this index and its potential to reduce TWOS episodes. [ABSTRACT FROM AUTHOR]

Lycopene (Ly), the most common type of antioxidant in the majority of diet types, provides tolerance to ischemia/reperfusion injury. However, the underlying mechanism of the protective effects observed following Ly administration remains poorly investigated. The aim of the current study was to investigate whether Ly prevents damage to hypoxia/reoxygenation (HR)-induced H9C2 myocardioblasts in an autophagy-dependent manner. The levels of autophagic markers were detected using western blotting, the level of apoptosis was detected using western blotting and flow cytometry. The activation of autophagy was impaired via knockdown of the expression of 'microtubule-associated protein 1-light chain 3β (MAP1LC3B)' and 'Beclin 1'. After 16 h hypoxia, followed by 2 h reoxygenation, the expression levels of the microtubule-associated protein 1A/1B-light chain 3 (LC3) and ?eclin 1 autophagic biomarkers, and cell viability were reduced, whereas the percentage of apoptotic cells, and the expression levels of the Bax/B-cell lymphoma 2 (Bcl-2) and active caspase-3 apoptotic biomarkers were increased. Pre-incubation of the cells with different Ly concentrations reversed the HR-induced inhibition of autophagy and cell viability, and the HR-induced elevation in apoptotic levels. The induction of autophagy was accompanied by reduced apoptosis, and decreased expression levels of Bax/Bcl-2 and active caspase-3. In addition, the impairment of autophagy by silencing the expression of MAP1LC3B and Beclin 1 accelerated HR-induced H9C2 cell apoptosis and the Ly-mediated protective effects disappeared. Furthermore, Bax/Bcl-2 and active caspase-3 expression levels were increased. Moreover, Ly-induced autophagy was associated with increased adenosine monophosphate kinase (AMPK) phosphorylation. Suppressed AMPK phosphorylation using compound C terminates Ly-mediated cytoprotective effects. Ly treatment improves cell viability and reduces apoptosis as a result of the activation of the adaptive autophagic response on HR-induced H9C2 myocardioblasts. AMPK phosphorylation may be involved in the progression. [ABSTRACT FROM AUTHOR]

To investigate the influence of breviscapine on the cardiac structure and function in diabetic cardiomyopathy rats as well as the expression of protein kinase C (PKC) and Ca-cycling proteins expression. Diabetes was induced in male Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin and the control rats were injected with saline. After the induction of diabetes for 4 weeks, the animals were divided into different groups: (1) normal rats as control; (2) diabetic rats; (3) diabetic rats with administration of breviscapine (10 or 25 mg kg day). After treatment with breviscapine for 6 weeks, the invasive cardiac function and echocardiographic parameters were measured, and heart tissue was obtained for electron microscope study. The expression of protein kinase C (PKC) and calcium handling regulators, such as protein phosphatase inhibitor-1 (PPI-1), phospholamban (PLB) and Ca-ATPase (SERCA-2), ryanodine receptor (RyR) were detected by western blot or RT-PCR. The activity of SERCA-2 was measured using Ca-ATPase kit. Diabetic rats showed impaired cardiac structure and function compared with control rats. The expression of PKC, PLB increased significantly, while the PPI-1, SERCA-2 and RyR expression decreased. Treatment with breviscapine could reverse the cardiac dysfunction and structure changes in diabetic cardiomyopathy rats, and decrease the expression of PKC and PLB, as well as increase the expression of PPI-1, SERCA-2 and RyR. The protective effect of breviscapine was dose related. This study showed that breviscapine could regulate the expression of PKC, PPI-1, PLB and SERCA-2 and have protective effect on diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that reduced endothelial progenitor subpopulation in lectin-binding and DiLDL-uptaking cell (EPC subpopulation) number and activity was associated with EPC subpopulation senescence that involved telomerase activity and telomere length. Stromal cell-derived factor-1α (SDF-1α) has been shown to augment a variety of cellular functions of EPC subpopulation and subsequently contribute to ischemic neovascularization. Therefore, we investigated whether SDF-1α might be able to prevent senescence of EPC subpopulation and also investigated the effects of SDF-1α on the telomerase activity and telomere length. EPC subpopulation were isolated from peripheral blood and characterized. After ex vivo prolonged cultivation, EPC subpopulation became senescent as determined by acidic β-galactosidase staining. SDF-1α dose-dependently inhibited the onset of EPC subpopulation senescence. Moreover, SDF-1α increased proliferation and colony-forming activity of EPC subpopulation. SDF-1α also increased telomerase activity and telomere length, which was accompanied with upregulation of the catalytic subunit, telomerase reverse transcriptase (TERT). Whereas these effects of SDF-1α on telomerase activity and expression of hTERT mRNA were significantly attenuated by CXCR4-specific peptide antagonist (AMD3100) and phosphoinositide 3-kinase (PI3K) inhibitor (LY294002). In conclusions, SDF-1α delays the onset of EPC subpopulation senescence, which may be related to the activation of telomerase and elongation of telomere length. The inhibition of EPC subpopulation senescence and induction of EPC subpopulation proliferation by SDF-1α in vitro may importantly improve the functional activity of EPC subpopulation for potential cell therapy. J. Cell. Physiol. 223:757–763, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

AbstractAim:To investigate the influence of breviscapine on high glucose-induced hypertrophy of cardiomyocytes and the relevant mechanism in vitro and in vivo.Methods:Cultured neonatal cardiomyocytes were divided into i) control; ii) high glucose concentrations; iii) high glucose+PKC inhibitor Ro-31-8220; iv) high glucose+breviscapine; or v) high glucose+NF-κB inhibitor BAY11–7082. Cellular contraction frequency and volumes were measured; the expression of protein kinase C (PKC), NF-κB, TNF-α, and c-fos were assessed by Western blot or reverse transcription-polymerase chain reaction (RT-PCR). Diabetic rats were induced by a single intraperitoneal injection of streptozotocin, and randomly divided into i) control rats; ii) diabetic rats; or iii) diabetic rats administered with breviscapine (10 or 25 mg·kg−1·d−1). After treatment with breviscapine for six weeks, the echocardiographic parameters were measured. All rats were then sacrificed and heart tissue was obtained for microscopy. The expression patterns of PKC, NF-κB, TNF-α, and c-fos were measured by Western blot or RT-PCR.Results:Cardiomyocytes cultured in a high concentration of glucose showed an increased pulsatile frequency and cellular volume, as well as a higher expression of PKC, NF-κB, TNF-α, and c-fos compared with the control group. Breviscapine could partly prevent these changes. Diabetic rats showed relative cardiac hypertrophy and a higher expression of PKC, NF-κB, TNF-α, and c-fos; treatment with breviscapine could ameliorate these changes in diabetic cardiomyopathy.Conclusion:Breviscapine prevented cardiac hypertrophy in diabetic rats by inhibiting the expression of PKC, which may have a protective effect in the pathogenesis of diabetic cardiomyopathy via the PKC/NF-κB/c-fos signal transduction pathway.Acta Pharmacologica Sinica (2009) 30: 1081–1091; doi: 10.1038/aps.2009.95; published online 13 July 2009 [ABSTRACT FROM AUTHOR]

Background aims Endothelial apoptosis underlies the pathophysiology of pulmonary arterial hypertension (PAH). Some factors/cytokines released by endothelial progenitor cells (EPC) have been revealed as potent inhibitors of apoptosis. The aim of this study was to investigate the effects of EPC on pulmonary microvascular endothelial cell (PMVEC) survival with the PAH condition. Methods PMVEC apoptosis was induced by high shear stress (HSS) with serum starvation or pro-inflammatory factors in an artificial capillary system. EPC were delivered into monocrotaline-induced PAH nude rats. Results PMVEC apoptosis under HSS and serum starvation conditions was significantly inhibited by EPC conditioned medium (CM). It was attenuated by vascular endothelial growth factor (VEGF)-A or -B blocking. EPC CM promoted PMVEC proliferation, which was weakened by VEGF-A or interleukin (IL)-8 blocking. The EPC CM caused less apoptosis of PMVEC induced by HSS plus pro-inflammatory factors. The anti-apoptotic effect of EPC CM was attenuated by blockade of either vascular endothelial growth factor receptor (VEGFR)-1 or -2. However, the pro-proliferating effect appeared to be weakened only by VEGFR-2 blocking. Both Erk1/2 and Akt phosphorylation were enhanced by EPC CM. VEGFR-2 blockage led to significant inhibition of Erk1/2 and Akt activation; VEGFR-1 blockage only of Erk1/2 activation. Human-origin VEGF co-localized with incorporated EPC in small pulmonary arterioles, and EPC transplantation resulted in down-regulation of caspase-3 expression. Conclusions The VEGF-A/B-VEGFR-1/2-Erk1/2 signal pathway took major responsibility for the anti-apoptotic effects of EPC on PMVEC, and VEGF-A-VEGFR-2-Akt for pro-proliferating effects. Growth factors, secreted in a paracrine manner by transplanted EPC, inhibited cell apoptosis in PAH lung. [ABSTRACT FROM AUTHOR]

Aim: The recruitment of endothelial progenitor cells (EPC) to ischemia has recently been suggested as an important mechanism of tissue repair. Although tissue ischemia can facilitate EPC mobilization, recruitment, and retention at the hypoxic site, the effects of hypoxia on EPC survival are not well known. In the present study, we examined whether hypoxia (2% O2) would suppress apoptosis induced by serum withdrawal and whether survival signals, such as the phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated protein kinase (ERK) pathways, were involved in this process. Methods: After being serum-starved for 24 h, EPC were cultured under normoxic or hypoxic conditions (2% O2) for 24 h. Cell survival was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, annexin V–propidium iodide dual-color flow cytometry, and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling assay. The expressions of signaling proteins were evaluated by Western blot analysis. Results: Under hypoxic conditions, EPC were resistant to apoptosis induced by serum starvation. The inhibition of the PI3K/Akt pathway using the LY294002 inhibitor prevented hypoxia-inhibited apoptosis in EPC and altered the phosphorylation state of glycogen synthase kinase-3β, an effector protein involved in regulation of EPC apoptosis. However, ERK inhibitor PD98059 had no significant effect on cell survival. Conclusion: Our data demonstrated that hypoxia inhibited serum withdrawal-induced apoptosis in EPC, which might be associated with the activation of the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]