Relationship between red blood cell-related indices and coronary artery calcification.

BACKGROUND: Red blood cell (RBC) indices such as RBC count and RBC distribution width (RDW) are associated with heart failure and coronary artery disease, but the relationship between RBC indices and coronary artery calcification (CAC) is unclear. This study aimed to investigate RBC indices' correlation with, and predictive value for, the presence and severity of CAC. METHODS: In this study, 1257 hospitalized patients who received a coronary computed tomography angiography examination were finally selected. Patients were classified into a control group (without CAC, n = 655) and a calcification group (with CAC, n = 602) according to their CAC score. The calcification group was further divided into a low calcification group, medium calcification group, and high calcification group. RESULTS: In the calcification group, the RBC count was lower, and the RDW-standard deviation (SD) and RDW-coefficient of variation (CV) were higher, than those in the control group (P < .05). In the high calcification group, the RBC count was significantly lower, and the RDW-SD and RDW-CV were significantly higher, than those in the low calcification group (P < .05). Multivariate logistic regression analysis showed that RBC count, RDW-SD, and RDW-CV were independent predictors of CAC presence. Furthermore, multivariate logistic regression analysis also showed that RBC count and RDW-SD were independent predictors of severe CAC. CONCLUSIONS: RBC indices were significantly associated with the presence and severity of CAC, indicating that these RBC indices have the potential to be predictors of CAC.

Epidemiological and clinical characteristics of 70 cases of coronavirus disease and concomitant hepatitis B virus infection: A multicentre descriptive study.

The interaction between existing chronic liver diseases caused by hepatitis B virus (HBV) infection and COVID-19 has not been studied. We analysed 70 COVID-19 cases combined with HBV infection (CHI) to determine the epidemiological, clinical characteristics, treatment and outcome. We investigated clinical presentation, imaging and laboratory parameters of COVID-19 patients of seven hospitals from Jan 20 to March 20, 2020. Multivariate analysis was used to analyse risk factors for progression of patients with COVID-19 combined with HBV infection. Compared with COVID-19 without HBV infection (WHI) group, patients with dual infection had a higher proportion of severe/critically ill disease (32.86% vs. 15.27%, P = .000), higher levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and activated partial thromboplastin (APTT) [50(28-69)vs 21(14-30), P = .000; 40(25-54) vs 23(18-30), P = .000; 34.0(27.2-38.7) vs 37.2(31.1-41.4), P = .031]. The utilization rates of Arbidol and immunoglobulin were significantly higher than those in the co-infected group [48.57% vs. 35.64%, P < .05; 21.43% vs. 8.18%, P < .001], while the utilization rate of chloroquine phosphate was lower (1.43% vs 14.00%, P < .05) in the co-infected patients group. Age and c-reactive protein (CRP) level were independent risk factors for recovery of patients with COVID-19 combined with HBV infection. The original characteristics of COVID-19 cases combined with HBV infection were higher rate of liver injury, coagulation disorders, severe/critical tendency and increased susceptibility. The elderly and patients with higher level of CRP were more likely to experience a severe outcome of COVID-19.

Obesity paradox in pulmonary hypertension due to left ventricular systolic dysfunction.

OBJECTIVE: Pulmonary hypertension (PH) due to left ventricular systolic dysfunction (PH-HFrEF) is a common heart disease with poor prognosis. In this study, we explored the risk factors for PH-HFrEF and investigated the related factors affecting the prognosis of PH-HFrEF patients. METHODS: The study recruited consecutive patients with PH-HFrEF and systolic pulmonary artery pressure (sPAP) of more than 40 mm Hg with left ventricular ejection fraction (LVEF) of less than 45% on echocardiography. Patients with left ventricular systolic dysfunction (HFrEF) but without PH (sPAP < 30 mmHg and LVEF < 45%) were chosen as the control group. Patients were followed up for 18 months, and major adverse cardiac events (MACE) were recorded. RESULTS: In total, 93 patients with PH-HFrEF formed the study group and 93 LVEF-matched patients with HFrEF were enrolled as controls. Body mass index (BMI) in PH-HFrEF patients was significantly lower compared with the control group (p < 0.05). Multivariate logistic regression analysis revealed that low BMI was an independent predictor of the presence of PH in patients with HFrEF (p < 0.05). There were 23 (24.7%) MACE in the PH-HFrEF group and 18 (19.4%) MACE in the control group. Cox regression analysis showed that low BMI was an independent predictor of MACE occurrence in the PH-HFrEF group (p < 0.05). CONCLUSION: Low BMI appear to be significantly associated with PH occurrence in patients with HFrEF, and is an independent predictor of MACE in patients with PH-HFrEF.

Relationship between soluble Semaphorin4D and cognitive impairment in patients with obstructive sleep apnea-hypopnea syndrome.

To investigate the relationship between plasma soluble semaphorin4D (sSema4D) and obstructive sleep apnea-hypopnea syndrome (OSAHS), and to ascertain the effect of sSema4D on cognitive dysfunction in patients with OSAHS. We prospectively recruited 30 men with moderate-severe OSAHS diagnosed by polysomnography, and 30 healthy controls with matched gender, age and education level. Montreal Cognitive Assessment (MoCA) was administered to determine cognitive impairment. Plasma sSema4D levels were measured. Among the total of 60 study patients, the overall plasma sSema4D level was 7.81 ± 1.91 ng/ml. Plasma sSema4D level in OSAHS group was significantly higher than that in controls (8.92 ± 1.79 vs 6.70 ± 1.28 ng/ml, p < 0.001). In OSAHS subgroup, patients with cognition impairment (CI) had higher plasma sSema4D level (10.50 ± 1.16 vs 8.00 ± 1.41 ng/ml, p < 0.001) and apnea-hypopnea index (AHI) (48.1 ± 14.0 vs 30.3 ± 9.2, p < 0.001) than those in non-CI group. Multiple logistic regression revealed that plasma sSema4D level (AOR 2.824, 95 % CI 1.562-5.103; p = 0.001) and BMI (AOR 2.237, 95 % CI 1.345-3.722; p = 0.002) were significantly associated with OSAHS, and plasma sSema4D was a significant predictor of CI after adjustment for other confounders (AOR 4.956, 95 % CI 1.581-15.538; p = 0.006). OSAHS patients, especially those with cognition impairment, are featured by elevated plasma sSema4D level, and sSema4D is significantly associated with cognition impairment induced by OSAHS.

Relationship between severity of obstructive sleep apnea and adverse cardiac outcomes in non-diabetic patients presenting with myocardial infarction.

Previous studies that have reported an association between obstructive sleep apnea and adverse cardiac events were confounded by a high prevalence of diabetes mellitus. We investigated the relationship between obstructive sleep apnea and the occurrence of major adverse cardiac events in non-diabetic patients who presented with ST-segment elevation myocardial infarction. A total of 41 patients who underwent overnight sleep screening within 5 days after admission for myocardial infarction from January 2007 to December 2008 were identified. Major adverse cardiac events-defined as a composite of cardiac death, non-fatal myocardial infarction, hospitalization for angina and congestive heart failure at 5-year follow-up-were determined. The patients were divided into two groups: those who experienced major adverse cardiac events and those who did not. In the overall cohort, the prevalence of obesity was 4.9 %. A total of 13 (31.7 %) patients had major adverse cardiac events. The mean apnea-hypopnea index was 25.4 ± 20.3. The group that experienced major adverse cardiac events had a higher apnea-hypopnea index than the group that did not (36.1 ± 21.0 vs 20.4 ± 18.2; P = 0.016). After adjusting for the resolution of ST-segment elevation and the use of a glycoprotein IIb/IIIa inhibitor, logistic regression analysis revealed that the apnea-hypopnea index remained an independent predictor of major adverse cardiac events (odds ratio 1.044; 95 % confidence interval 1.003-1.086; P = 0.033). In non-diabetic patients, the severity of obstructive sleep apnea was associated with the occurrence of major adverse cardiac events at 5-year follow-up after ST-segment elevation myocardial infarction.

Serum adropin level in patients with stable coronary artery disease.

OBJECTIVES: Adropin is a newly identified secreted protein implicated in the regulation of insulin sensitivity and vascular endothelial function. Recent studies have shown that lower serum adropin level is related to acute myocardial infarction and coronary atherosclerosis. The primary objective of this study was to ascertain the association of serum adropin level with stable coronary artery disease (SCAD). METHODS: We prospectively recruited a cohort of patients with SCAD and similar sample size subjects without coronary artery disease as controls. Their serum adropin levels were measured, and the severity of coronary atherosclerosis in SCAD patients was quantified with the syntax score. RESULTS: A total of 116 patients with SCAD and 116 control subjects without coronary artery disease were recruited. Patients with SCAD had lower serum adropin levels when compared with the controls (59.2±19.3 versus 70.0±18.2 pg/mL, P<0.001). The multiple logistic regression revealed that low serum adropin level was a significant predictor of SCAD (AOR 0.976, 95% CI 0.960-0.992; p=0.003). Through the gamma regression model, it was further revealed that serum adropin level is significantly associated with syntax score (coefficient: -0.134, 95% CI: -0.212- -0.056; p=0.001). CONCLUSIONS: Low serum adropin level is a significant predictor of SCAD. It is also associated with syntax score, thus indicating the close relationship between adropin and coronary atherosclerosis.

[Correlation of serum adropin level with coronary artery disease].

OBJECTIVE: To explore the correlation of serum adropin level with coronary artery disease (CAD). METHODS: According to coronary angiography, 356 consecutive patients with chest complaints from January 2011 to July 2012 were divided into 2 groups of CAD (n = 264, with CAD) and control (n = 92, without CAD). The serum adropin level and other CAD related metabolic parameters were measured and SYNTAX score was calculated. RESULTS: Serum adropin level was significantly lower in group CAD than that in control group ((56 ± 15) vs (83 ± 10) ng/L, P < 0.01).Serum adropin levels in high, mild, low SYNTAX score group were (60 ± 22),(56 ± 12),(54 ± 10) ng/L respectively, and there was no significant difference among 3 groups(P = 0.116). Multivariate regression analysis revealed that adropin was an independent risk factor for CAD (OR = 0.849, 95%CI:0.817-0.882, P < 0.01). CONCLUSIONS: Lower serum adropin level is significantly associated with CAD. Thus it indicates a possible role of adropin in the prevention of CAD.

Adropin - A new player in energy regulation predicts long-term prognosis of patients with acute myocardial infarction.

Background: As a novel energy homeostasis regulator, Adropin not only plays a vital part in meditating energy metabolism, but also has a certain correlation with atherosclerotic diseases. The purpose of this study was to evaluate the effect of Adropin on the long-term prognosis of patients with acute myocardial infarction (AMI). Methods: 162 recruited patients with AMI were divided into low Adropin group (Adropin<166.3 pg/mL, n = 82) and high Adropin group (Adropin≥166.3 pg/mL, n = 80), according to the mean value of serum Adropin level. Patients were followed up and major adverse cardiac events (MACEs) were recorded. The Kaplan-Meier method and Cox regression model were used to evaluate the survival of patients and the related factors of cardiac events. Results: Diabetes was more common in low Adropin group than that in high Adropin group (P < 0.05). Patients were followed up for an average of 50.3 ± 19.2 months. MACEs occurred in 37 patients (22.8%), including 6 cardiac deaths (3.7%), 14 recurrent myocardial infarction (8.6%) and 17 rehospitalization of heart failure (10.5%). The incidence of recurrent myocardial infarction in low Adropin group was higher than that in high Adropin group (13.4% vs 3.8%, P < 0.05). There was no significant difference in the overall incidence of MACE, cardiac death and rehospitalization of heart failure between the two groups. Kaplan-Meier method (log rank test) analysis results showed that patients with low Adropin had lower survival rate without recurrent myocardial infarction (log rank P = 0.035). Conclusion: Low Adropin level was associated with an increased risk of long-term recurrent myocardial infarction in patients with AMI.

Adropin Inhibits Vascular Smooth Muscle Cell Osteogenic Differentiation to Alleviate Vascular Calcification via the JAK2/STAT3 Signaling Pathway.

Vascular calcification is characterized as the deposition of hydroxyapatite mineral in the form of calcium-phosphate complexes in the vasculature. Transdifferentiation between vascular smooth muscle cells (VSMCs) and osteoblast-like cells is considered essential in the progression of vascular calcification. The pathophysiological mechanisms underlying vascular calcification and VSMC osteogenic differentiation remain to be fully elucidated, and the development of novel therapies is required. In the present study, PCR and western blot analysis were conducted to quantify the mRNA and protein expression levels of calcification-associated markers (bone morphogenetic protein 2, alkaline phosphatase, osteoprotegerin, osteocalcin, and runt-related transcription factor 2) and adropin in VSMCs and rat vascular tissues. The calcification of VSMCs was assessed using alizarin red staining. Moreover, adropin expression levels in VSMCs were analyzed using immunofluorescence. Lentiviral transfection and small interfering RNA were used for overexpression and knockdown of adropin in VSMCs, respectively. The results demonstrated that adropin alleviated vascular calcification in vivo. Moreover, adropin also inhibited osteogenic differentiation and the calcification of VSMCs in vitro. Notably, results of the present study revealed that the tyrosine protein kinase JAK2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway played a key role in the aforementioned inhibition. In conclusion, the results of the present study demonstrated that adropin inhibited VSMC osteogenic differentiation to alleviate vascular calcification via the JAK2/STAT3 signaling pathway.

Puerarin alleviates coronary heart disease via suppressing inflammation in a rat model.

BACKGROUND: Puerarin shows inhibitory effects on inflammation in chronic heart failure (CHF), but its efficacy in coronary heart disease (CHD) remained vague. METHODS: Rat CHD model was constructed, and serum parameters were determined using a blood liquid biochemical analyzer. Also, contents of creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin (cTnT) were measured using colorimetry. Histological examination was conducted with Hematoxylin-Eosin (H&E) staining, and cardiac function was assessed by Echocardiography. Cell apoptosis was detected using Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Relative expressions were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. RESULTS: In CHD rats, the levels of TC, LDL and TG and the expressions of matrix metalloproteinase-9 (MMP-9), CD40 ligand (CD40L), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were increased while HDL level was decreased, accompanied with inflammatory cell infiltration and cardiac malfunction. Also, the contents of CK, CK-MB, LDH and cTnT, the percentage of apoptotic cells, the expressions of Bcl-2 associated X protein (Bax), cleaved Caspase-3, TNF-α, Interleukin-ß (IL-ß), IL-6 and Lipoprotein-associated Phospholipase A2 (Lp-PLA2) expressions and the levels of oxidized-(ox-)LDL and malondialdehyde (MDA) were upregulated, while the level of super oxidase dismutase (SOD) and the expressions of B cell lymphoma-2 (Bcl-2) and vascular endothelial growth factor (VEGF) were downregulated. However, Puerarin ameliorated the effects of CHD model construction, suppressed nuclear factor-(NF-)κB expression, and enhanced the expressions of Farnesoid X Receptor (FXR), phosphorylated-AKT (p-AKT) and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3). CONCLUSION: Puerarin alleviated CHD in rats via inhibiting inflammation, providing possible method for CHD treatment.

Association of cystatin C with coronary artery calcification in patients undergoing multidetector computed tomography.

ABSTRACT: Cystatin C is associated with atherosclerosis, but the relationship between cystatin C and coronary artery calcification (CAC) is uncertain. The purpose of this study was to evaluate the predictive value of cystatin C on the occurrence and severity of CAC.A total of 1447 hospitalized patients with coronary computed tomography angiography were selected in this study. According to the CAC score (CACS), patients were divided into calcification group (with CAC, n = 749) and control group (without CAC, n = 698). The calcification group was further divided into low calcification group (CACS < 100, n = 407), medium calcification group (CACS 100-400, n = 203), and high calcification group (CACS≥400, n = 139).Patients with CAC had higher cystatin C level than those in control group (P < .05). With the increase of calcification score, the cystatin C level showed an upward trend. The cystatin C level in the high calcification group was significantly higher than those in the low and medium calcification group (P < .05). ROC curve analysis showed that cystatin C had a high predictive value for the occurrence of CAC [area under the curve 0.640, 95% confidence interval (95% CI) 0.591-0.690, cut-off value 0.945 mg/L, sensitivity 0.683, specificity 0.558, P < .05] and severe CAC (area under the curve 0.638, 95% CI 0.550-0.762, cut-off value 0.965 mg/L, sensitivity 0.865, specificity 0.398, P < .05). Multivariate logistic regression analysis showed that cystatin C was an independent predictor of severe CAC (AOR 3.748, 95% CI 1.138-10.044, P < .05).Cystatin C was significantly associated with the occurrence and severity of CAC, suggesting that cystatin C had the potential as a predictor of CAC.

Adropin inhibits the phenotypic modulation and proliferation of vascular smooth muscle cells during neointimal hyperplasia by activating the AMPK/ACC signaling pathway.

In-stent restenosis (ISR) remains an inevitable problem for some patients receiving drug-eluting stent (DES) implantation. Intimal hyperplasia is an important biological cause of ISR. It has been previously reported that adropin is a potentially protective factor in cardiovascular disease. Therefore, the present study investigated the function of adropin in inhibiting smooth muscle cell (SMC) phenotype modulation and proliferation, causing intimal hyperplasia. A total of 56 patients who visited the hospital consecutively (25 with ISR and 31 without ISR), who were followed up between April 2016 and March 2019, 1 year following DES, were analyzed to evaluate the association between in-stent neointimal volume and adropin serum levels. Rat aorta smooth muscle cells (RASMCs) were used to determine the effects of adropin on their phenotypic modulation and proliferation using western blot, MTT, PCR and immunofluorescence analyses. Adropin serum levels in the ISR group were significantly lower than those in the non-ISR group. Furthermore, linear regression analysis revealed that only adropin levels were negatively associated with neointimal volume in both groups. The overall adropin levels of the 56 patients and the percentages of neointimal volume revealed a strong negative association. In vitro, adropin suppressed angiotensin II (Ang II)-induced phenotypic modulation in RASMCs by restoring variations of osteopontin and α-smooth muscle actin. Furthermore, compared with the Ang II group, adropin markedly decreased the percentage of G2/M-phase cells. Finally, adropin negatively regulated the phenotypic modulation and proliferation of RASMCs via the AMP-activated protein kinase/acetyl-CoA carboxylase (AMPK/ACC) signaling pathway. In conclusion, an independent, negative association was revealed between adropin and intimal hyperplasia; specifically, adropin inhibited the phenotypic modulation and proliferation of RASMCs by activating the AMPK/ACC signaling pathway. Therefore, adropin may be used as a potential predictor and therapeutic target for intimal hyperplasia and ISR.

The protective role of DPP4 inhibitors in atherosclerosis.

Diabetes is a chronic non-communicable disease whose incidence continues to grow rapidly, and it is one of the most serious and critical public health problems. Diabetes complications, especially atherosclerosis-related chronic vascular complications, are a serious threat to human life and health. Growing evidence suggests that dipeptidyl peptidase 4 (DPP4) inhibitors, beyond their role in improving glycemic control, are helpful in ameliorating endothelial dysfunction in humans and animal models of T2DM. In fact, DPP4 inhibitors have been shown by successive studies to play a protective effect against vascular complications. On one hand, in addition to their hypoglycemic effects, DPP4 inhibitors participate in the control of atherosclerotic risk factors by regulating blood lipids and lowering blood pressure. On the other hand, DPP4 inhibitors exert anti-atherosclerotic effects directly through multiple mechanisms, including improving endothelial cell dysfunction, increasing circulating endothelial progenitor cell (EPCs) levels, regulating mononuclear macrophages and smooth muscle cells, inhibiting inflammation and oxidative stress and improving plaque instability. Herein, we review the beneficial roles of DPP4 inhibitors in atherosclerosis as detailed.

Prediction of COVID-19 Patients at High Risk of Progression to Severe Disease.

In order to develop a novel scoring model for the prediction of coronavirus disease-19 (COVID-19) patients at high risk of severe disease, we retrospectively studied 419 patients from five hospitals in Shanghai, Hubei, and Jiangsu Provinces from January 22 to March 30, 2020. Multivariate Cox regression and orthogonal projections to latent structures discriminant analysis (OPLS-DA) were both used to identify high-risk factors for disease severity in COVID-19 patients. The prediction model was developed based on four high-risk factors. Multivariate analysis showed that comorbidity [hazard ratio (HR) 3.17, 95% confidence interval (CI) 1.96-5.11], albumin (ALB) level (HR 3.67, 95% CI 1.91-7.02), C-reactive protein (CRP) level (HR 3.16, 95% CI 1.68-5.96), and age ≥60 years (HR 2.31, 95% CI 1.43-3.73) were independent risk factors for disease severity in COVID-19 patients. OPLS-DA identified that the top five influencing parameters for COVID-19 severity were CRP, ALB, age ≥60 years, comorbidity, and lactate dehydrogenase (LDH) level. When incorporating the above four factors, the nomogram had a good concordance index of 0.86 (95% CI 0.83-0.89) and had an optimal agreement between the predictive nomogram and the actual observation with a slope of 0.95 (R2 = 0.89) in the 7-day prediction and 0.96 (R2 = 0.92) in the 14-day prediction after 1,000 bootstrap sampling. The area under the receiver operating characteristic curve of the COVID-19-American Association for Clinical Chemistry (AACC) model was 0.85 (95% CI 0.81-0.90). According to the probability of severity, the model divided the patients into three groups: low risk, intermediate risk, and high risk. The COVID-19-AACC model is an effective method for clinicians to screen patients at high risk of severe disease.

Circular RNA hsa_circ_0000515 acts as a miR-326 sponge to promote cervical cancer progression through up-regulation of ELK1.

This study investigates the role of circular RNA (circRNA) hsa_circ_0000515 in cervical cancer and the underlying mechanism associated with microRNA-326 (miR-326). hsa_circ_0000515 and ETS transcription factor ELK1 (ELK1) were initially over-expressed and miR-326 was down-regulated in cervical cancer tissues and cells. Low hsa_circ_0000515 expression was found to be associated with favorable prognosis of patients with cervical cancer. A series of mimics, inhibitors, over-expression plasmids or siRNAs were introduced into cervical cancer cells to alter the expression of hsa_circ_0000515, miR-326 and ELK1. In vitro experiments exhibited that silencing of hsa_circ_0000515 or upregulation of miR-326 resulted in suppressed proliferation and invasion, along with induced apoptosis and autophagy of cervical cancer cells. Dual-luciferase reporter assay, RNA pull-down and RIP assays highlighted that hsa_circ_0000515 was able to act as a ceRNA of miR-326 to increase ELK1. Furthermore, enhancement of ELK1 expression resulted in enhanced proliferation and invasion but repressed apoptosis and autophagy of cervical cancer cells. In vivo experiments further confirmed the suppressed tumor growth by hsa_circ_0000515 silencing. Our findings demonstrated that hsa_circ_0000515 acts as a tumor promoter in cervical cancer. The study provides evidence for targeting hsa_circ_0000515 for therapeutic purposes in treating cervical cancer.

Ginkgolide B ameliorates myocardial ischemia reperfusion injury in rats via inhibiting endoplasmic reticulum stress.

PURPOSE: Ginkgolide B (GB) is a terpene lactone component found in Ginkgo biloba, which has a protective role on ischemia reperfusion (I/R) injury. This study was aimed at exploring the protective mechanism of GB on the myocardial I/R. PATIENTS AND METHODS: Myocardial I/R model was established on Sprague Dawley rats. The levels of cardiac troponin I, cardiac troponin T, lactic dehydrogenase, and myoglobin were determined by a 200FR NEO automatic biochemical analyzer. Histological examination was performed through HE and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining. The expression levels of p-PERK, p-IRE1α, ATF6, p-AKT, and mTOR were detected by Western blot. RESULTS: The results exhibited that GB treatment suppressed the high levels of cardiac troponin I, cardiac troponin T, lactic dehydrogenase, and myoglobin and ameliorated the damaged and irregularly arranged myocardial cells induced by I/R injury significantly, indicating that GB could ameliorate myocardial I/R injury. Moreover, the high expression levels of endoplasmic reticulum (ER) stress key proteins caused by I/R injury were suppressed significantly by GB treatment, including p-PERK, p-IRE1α, and ATF6. GB treatment also decreased the number of apoptotic cells compared with I/R group. In addition, activation of ER stress by Tunicamycin treatment could counteract the protective effects of GB on I/R injury, suggesting that GB ameliorated myocardial I/R injury through inhibition of ER stress-induced apoptosis. Finally, the decreased p-AKT and p-mTOR expressions caused by I/R injury were upregulated by GB and inhibition of PI3K/AKT/mTOR pathway by LY294002 abolished the protective effects of GB on I/R injury, indicating that GB activated PI3K/AKT/mTOR pathway during I/R injury. CONCLUSION: GB protected against myocardial I/R injury through inhibiting ER stress-induced apoptosis via PI3K/AKT/mTOR signaling pathway.

Effect of beraprost on pulmonary hypertension due to left ventricular systolic dysfunction.

Beraprost is used to treat peripheral chronic arterial occlusive disease. However, the efficacy and safety of beraprost in patients with pulmonary hypertension (PH) due to left ventricular systolic dysfunction (PH-HFrEF) remains unknown. The primary objective of this study was to determine the effects of beraprost on PH-HFrEF.We prospectively recruited patients with PH-HFrEF as determined by echocardiography and right cardiac catheterization. Beraprost sodium was given orally (1 µg/kg/d) added to the usual treatment, and patients were evaluated at 1-year follow-up.Twenty-five patients were recruited with baseline systolic pulmonary artery pressure (PAP) of 49.5 ±â€Š10.8 mm Hg. Systolic PAP results at 3, 6, 9, and 12 months were 39.1 ±â€Š8.1, 30.4 ±â€Š5.2, 27.7 ±â€Š3.0, and 27.0 ±â€Š4.7 mm Hg, respectively, which were all significantly lower than systolic PAP at baseline (P < .05). Left ventricular ejection fraction results at 6 months (43.5 ±â€Š7.0%), 9 months (47.0 ±â€Š5.5%), and 12 months (48.2 ±â€Š4.8%) were significantly higher than at baseline (34.7 ±â€Š9.2%) (P < .05). Six-minute walking distance at 3 months (282.8 ±â€Š80.6 m), 6 months (367.1 ±â€Š81.2 m), 9 months (389.8 ±â€Š87.1 m), and 12 months (395.7 ±â€Š83.4 m) increased with time, and all were significantly higher than baseline (190.1 ±â€Š75.5 m) (P < .05). One patient developed atrial fibrillation and recovered to sinus rhythm after intravenous administration of amiodarone. There were no instances of cardiac-related death, severe bleeding, or severe impairment of liver function.Routine oral administration of beraprost sodium added to the usual treatment may improve cardiopulmonary hemodynamics and exercise capacityin patients with PH-HFrEF.

The effect of RhoA on human umbilical vein endothelial cell migration and angiogenesis in vitro.

The mechanisms that control the morphologic organization of endothelial cells (ECs) into new blood vessels are not well understood. Recent studies revealed that the small G proteins of the Rho family are key regulators of cell migration, involving reorganization of the actin cytoskeleton, cell migration and the regulation of gene transcription. We hypothesized that RhoA GTPase, a member of the Rho family, may play an important role in EC organization during angiogenesis, the process of new vessel formation in pre-existing tissues. To test this hypothesis, we investigated the effects of RhoA on human umbilical vein endothelial (HUVE) cell migration and angiogenesis in vitro, by stably transfecting HUVE cells with sense RhoA expression plasmid through the Lipofect-2000 system. Wound assay in vitro and 3-dimensional cell culture were used to detect the migration and angiogenesis capacity of HUVE cells. The morphological changes of transfected cells were revealed under confocal and phase contrast microscopy. Our results demonstrated that the increased expression of RhoA in HUVE cells significantly enhanced the morphogenetic changes and cytoskeletal reorganization of the transfected cells, and also enhanced cell migration and angiogenic capacity in vitro, suggesting that RhoA plays an important role in the process of HUVE cell migration and angiogenesis in vitro.