Phlorizin, a novel caloric restriction mimetic, stimulates hypoxia and protects cardiomyocytes through activating autophagy via modulating the Hif-1α/Bnip3 axis in sepsis-induced myocardial dysfunction.

BACKGROUND: Sepsis is a systemic inflammatory syndrome that can lead to multiple organ dysfunction and life-threatening complications. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to be present in half of patients with septic shock, increasing their mortality rate to 70-90%. The pathogenesis of SIMD is complex, and no specific clinical treatment has yet been developed. Caloric restriction mimetics (CRM), compounds that simulate the biochemical and functional properties of CR, can improve cardiovascular injury by activating autophagy. This study investigated the effect of a new type of CRM which can induce hypoxia, the SGLT nonspecific inhibitor phlorizin on SIMD. MATERIALS AND METHODS: In vivo, phlorizin was administered at 1 mg/kg/day intragastrically for 28 days. In vitro, AC16 was treated with 120 µM phlorizin for 48 h. Echocardiography was used to assess cardiac function. Myocardial injury markers were detected in serum and cell supernatant. Western blotting was employed to detect changed proteins associated with apoptosis and autophagy. Immunofluorescence, immunohistochemistry, co-immunoprecipitation, molecular docking, and other methods were also used to illustrate cellular changes. RESULTS: In vivo, phlorizin significantly improved the survival rate and cardiac function after sepsis injury, reduced markers of myocardial injury, inhibited myocardial apoptosis and oxidative stress, and promoted autophagy. In vitro, phlorizin alleviated the apoptosis of AC16, as well as inhibited oxidative stress and apoptotic enzyme activity. Phlorizin acts on autophagy at multiple sites through low energy (activation of AMPK) and hypoxia (release of Beclin-1 by Hif-1α/Bnip3 axis), promoting the formation and degradation of autophagosomes. CONCLUSION: We indicated for the first time that phlorizin could inhibit glucose uptake via GLUT-1 and conforms to the metabolic characteristics of CRM, it can induce the hypoxic transcriptional paradigm. In addition, it inhibits apoptosis and improves SIMD by promoting autophagy generation and unobstructing autophagy flux. Moreover, it affects autophagy by releasing Beclin-1 through the Hif-1α/Bnip3 axis.

3, 4-Benzopyrene (Bap) aggravated abdominal aortic aneurysm formation by targeting pyroptosis in smooth muscle cells through ET-1 mediated NLRP3-inflammasome activation.

According to epidemiological studies, smoking is one of the leading causes of the high incidence of abdominal aortic aneurysms (AAA).3,4-Benzopyrene (Bap) is a by-product of coal tar and tobacco combustion produced by the incomplete combustion of organic fuels. It is an essential component of both automobile exhaust and tobacco smoke, it is also an important member of the air pollutants. However, the exact mechanism by which Bap can worsen the condition of patients with AAA and increase the mortality of patients with AAA remains unknown. This research aims to investigate the role of Bap in inducing pyroptosis in AAA. In vitro experiments, we revealed that pyroptosis-Gasdermin D (GSDMD) increased when Bap was used. Additionally, the release of inflammatory factors, such as IL-1ß and IL-18 were also rising. An mRNA sequencing analysis revealed that macrophages expressed a high level of the endothelin gene when cells were stimulated by Bap. It seemed that smooth muscle cells pyroptosis was related to macrophages. Experiments revealed that endothelin could increase the calcium ion concentration in smooth muscle cells, resulting in a large amount of ROS and activation of NLRP3 inflammasomes. We discovered that treatment with endothelin receptor antagonist (ABT-546) in vivo and calcium ion chelator (BAPTA) in vitro decreased AAA diameter, downregulated NLRP3 inflammasomes and ROS, and significantly reduced the number of activated GSDMD. Inflammatory mediators were released at a lower level. These findings suggest that Bap-induced pyroptosis may be mediated by the ET-1-Ca2+-inflammasome pathway, providing a new way to reduce mortality in AAA patients.

3,4-benzo[a]pyrene aggravates myocardial infarction injury by activating NLRP3-related pyroptosis through PINK1/Parkin-mitophagy-mPTP opening axis.

BACKGROUND: Air pollution is an important and interventionable risk factor for cardiovascular disease. Air pollution exposure, even for a short-term exposure, is conspicuously relevant to increased risk of myocardial infarction (MI) mortality and clinical evidence has shown that air pollution particulate matter (PM) induces the aggravation of AMI. 3,4-benzo[a]pyrene (BaP), an extremely toxic polycyclic aromatic hydrocarbon (PAH) and a common component of PM, is listed as one of the main objects of environmental pollution monitoring. Both epidemiological and toxicological studies suggest that BaP exposure may be associated with cardiovascular disease. Since PM is significantly associated with the increased risk of MI mortality, and BaP is an important component of PM associated with cardiovascular disease, we intend to investigate the effect of BaP on MI models. METHODS: The MI mouse model and the oxygen and glucose deprivation (OGD) H9C2 cell model were used to investigate the effect of BaP in MI injury. The involvement of mitophagy and pyroptosis in regulating deterioration of cardiac function and aggravation of MI injury induced by BaP was comprehensively evaluated. RESULTS: Our study shows that BaP exacerbates MI injury in vivo and in vitro, a result based on BaP-induced NLRP3-related pyroptosis. In addition, BaP can inhibit PINK1/Parkin dependent mitophagy through the aryl hydrocarbon receptor (AhR), thus the mitochondrial permeability transition pore (mPTP) was induced to open. CONCLUSION: Our results suggest a role for the BaP from air pollution in MI injury aggravation and reveal that BaP aggravates MI injury by activating NLRP3-related pyroptosis via the PINK1/Parkin-mitophagy-mPTP opening axis.

3,4-benzopyrene aggravates myocardial ischemia-reperfusion injury-induced pyroptosis through inhibition of autophagy-dependent NLRP3 degradation.

Polycyclic aromatic hydrocarbons (PAHs) are produced during combustion of organic matter, such as during cigarette smoking, and they exist widely in the environment. Exposure to 3,4-benzo[a]pyrene (BaP), as the most widely studied PAHs, relates to many cardiovascular diseases. However, the underlying mechanism of its involvement remains largely unclear. In this study, we developed a myocardial ischemia-reperfusion (I/R) injury mouse model and an oxygen and glucose deprivation-reoxygenation H9C2 cell model to evaluate the effect of BaP in I/R injury. After BaP exposure, the expression of autophagy-related proteins, the abundance of NLRP3 inflammasomes, and the degree of pyroptosis were measured. Our results show that BaP aggravates myocardial pyroptosis in a autophagy-dependent manner. In addition, we found that BaP activates the p53-BNIP3 pathway via the aryl hydrocarbon receptor to decrease autophagosome clearance. Our findings present new insights into the mechanisms underlying cardiotoxicity and reveal that the p53-BNIP3 pathway, which is involved in autophagy regulation, is a potential therapeutic target for BaP-induced myocardial I/R injury. Because PAHs are omnipresent in daily life, the toxic effects of these harmful substances should not be underestimated.

Shexiang Baoxin Pill attenuates myocardial ischemia/reperfusion injury by activating autophagy via modulating the ceRNA-Map3k8 pathway.

BACKGROUND: The pathogenesis of myocardial ischemia/reperfusion is complex, involving multiple regulatory genes and environmental factors, and requiring the simultaneous regulation of multiple targets. Meanwhile, Traditional Chinese Medicine (TCM) has certain advantages in the comprehensive treatment of multi-site, multi-target conditions and overall regulation of this condition. This study explores the effect of the well-known TCM, the Shexiang Baoxin Pill (SBP) on myocardial ischemia/reperfusion injury in mice. MATERIALS AND METHODS: In vivo, 20 mg/kg/day SBP was administered by gavage for 28 days. In vitro, cardiomyocytes were pretreated with 25 µg/ml SBP for 24 h. Evans blue/TTC double-staining was employed to determine the infarct size. Markers of myocardial injury were detected in the serum and cell supernatants. The changes of pyroptosis and autophagy proteins were detected by western blot. Immunofluorescence, immunohistochemistry and PCR were performed to further illustrate the results. RESULTS: SBP significantly reduced the myocardial infarct size, decreased the myocardial injury markers, inhibited cardiomyocyte pyroptosis and oxidative stress, and promoted autophagy in vivo. In vitro, SBP alleviated cardiomyocyte pyroptosis, inhibited oxidative stress, reduced IL-1ß and IL-18 secretion, and unblocked autophagy flux. Myocardial injury is mitigated by SBP via the rapid degradation of autophagosomes, and SBP promotes the accumulation of autophagosomes by downregulating mmu_circ_0005874, Map3k8 and upregulating mmu-miR-543-3p. CONCLUSION: We found for the first time that SBP can inhibit pyroptosis and oxidative stress, and protect from myocardial I/R injury. In addition, it inhibits pyroptosis and improves H/R injury by promoting autophagosome generation and accelerating autophagic flux. SBP interferes with autophagy through the interaction between mmu_circ_0005874/mmu-miR-543-3p/Map3k8.

A Single, Acute Astragaloside IV Therapy Protects Cardiomyocyte Through Attenuating Superoxide Anion-Mediated Accumulation of Autophagosomes in Myocardial Ischemia-Reperfusion Injury.

Myocardial ischemia-reperfusion (I/R) injury, characterized by myocardial cell death (e.g., apoptosis) and generation of reactive oxygen species (ROS) such as superoxide (O2 ·-) and hydrogen peroxide (H2O2), is a serious threat to human health and property. Saponin astragaloside IV (ASIV), extracted from Chinese herbal medicine astragalus, is effective in resolving multiple pathological issues including myocardial I/R injury. Recent studies have shown that autophagy is regulated by ROS and plays an important role in myocardial I/R injury. However, regulation of autophagy by ASIV during myocardial I/R injury and the role of specific ROS involved in the process have been rarely reported. In the present study, we found that SOD2 was downregulated and O2 ·- was upregulated in H2O2-induced H9C2 cardiac myocyte injury in vitro and myocardial I/R injury in vivo, while such alterations were reversed by ASIV. ASIV possessed the ability to alleviate myocardial I/R injury via attenuating I/R-caused autophagosome accumulation. Upregulate of O2 ·- by 2-methoxyestradiol (2-ME) reversed the effect of ASIV-mediated autophagy regulation, which suggested that O2 ·- was vital in this process. In conclusion, our results contribute to understanding the mechanism of ASIV-induced cardioprotective effect.

Sodium-Glucose Co-transporter-2 Inhibitor of Dapagliflozin Attenuates Myocardial Ischemia/Reperfusion Injury by Limiting NLRP3 Inflammasome Activation and Modulating Autophagy.

Background: The sodium-glucose co-transporter-2 (SGLT-2) inhibitor dapagliflozin improves cardiovascular outcomes in patients with type 2 diabetes in a manner that is partially independent of its hypoglycemic effect. These observations suggest that it may exert a cardioprotective effect by another mechanism. This study explored the effects of dapagliflozin on myocardial ischemia/reperfusion injury in a mouse model. Materials and Methods: For the in vivo I/R studies, mice received 40 mg/kg/d dapagliflozin, starting 7 days before I/R. Evans Blue/TTC double-staining was used to determine the infarct size. Serum levels of cTnI, CK-MB, and LDH were measured. Inflammation, autophagy protein expression, and caspase-1 activity changes were measured at the protein level. Primary cardiomyocytes were used to investigate the direct effect of dapagliflozin on cardiomyocytes and to verify whether they have the same effect as observed in in vivo experiments. Result: A high dose of dapagliflozin significantly reduced infarct size and decreased the serum levels of cTnI, CK-MB, and LDH. Dapagliflozin also reduced serum levels of IL-1ß, reduced expression of myocardial inflammation-related proteins, and inhibited cardiac caspase-1 activity. The treatment restored autophagy flux and promoted the degradation of autophagosomes. Relief of inflammation relied on autophagosome phagocytosis of NLRP3 and autophagosome clearance after lysosome improvement. 10 µM dapagliflozin reduced intracellular Ca2+ and Na+ in primary cardiomyocytes, and increasing NHE1 and NCX expression mitigated dapagliflozin effects on autophagy. Conclusion: Dapagliflozin protects against myocardial ischemia/reperfusion injury independently of its hypoglycemic effect. High-dose dapagliflozin pretreatment might limit NLRP3 inflammasome activation and mediate its selective autophagy. Dapagliflozin directly acts on cardiomyocytes through NHE1/NCX.

Screening and Identification of Potential Hub Genes in Myocardial Infarction Through Bioinformatics Analysis.

BACKGROUND: Myocardial infarction (MI) is a common cause of death worldwide. It is characterized by coronary artery occlusion that causes ischemia and hypoxia of myocardial cells, leading to irreversible myocardial damage. MATERIALS AND METHODS: To explore potential targets for treatment of MI, we reorganized and analyzed two microarray datasets (GSE4648 and GSE775). The GEO2R tool was used to screen for differentially expressed genes (DEGs) between infarcted and normal myocardium. We used the Database for Annotation, Visualization and Integrated Discovery (DAVID) to perform Gene Ontology functional annotation analysis (GO analysis) and the Kyoto Encyclopedia of Genes and Genomes for pathway enrichment analysis (KEGG analysis). We examined protein-protein interactions to characterize the relationship between differentially expressed genes, and we screened potential hub genes according to the degree of connection. PCR and Western blotting were used to identify the core genes. RESULTS: At different times of infarction, a total of 35 genes showed upregulation at all times; however, none of the genes showed downregulation at all 3 times. Similarly, 10 hub genes with high degrees of connectivity were identified. In vivo and in vitro experiments suggested that expression levels of MMP-9 increased at various times after myocardial infarction and that expression increased in a variety of cells simultaneously. CONCLUSION: Expression levels of MMP-9 increase throughout the course of acute myocardial infarction, and this expression has both positive and negative sides. Further studies are needed to explore the role of MMP-9 in MI treatment. The potential values of Il6, Spp1, Ptgs2, Serpine1, Plaur, Cxcl5, Lgals3, Serpinb2, and Cd14 are also worth exploring.

Metformin suppresses inflammation and apoptosis of myocardiocytes by inhibiting autophagy in a model of ischemia-reperfusion injury.

Metformin (Met) is a major widely used oral glucose lowering drug for the treatment of type 2 diabetes. It is reported that metformin could regulate autophagy in various diseases of cardiovascular system including in I/R injury, diabetic cardiomyopathy and heart failure. Autophagy plays a controversial role in ischemia/reperfusion (I/R) injury, and this research was performed to explore the cardioprotective effect of Met on I/R injury and discuss the underlying mechanism of autophagy in it. In vivo and in vitro, Met exerted cardioprotection function of decreasing myocardial inflammation and apoptosis with a decrease in the level of autophagy. Moreover, Met significantly inhibited autophagosome formation and restore the impairment of autophagosome processing, which lead to cardioprotection effect of Met. Akt was up-regulated in Met-treated I/R hearts and miransertib, a pan-AKT inhibitor, was able to reverse the alleviating autophagy effect of Met. We demonstrate that Met protects cardiomyocytes from I/R-induced apoptosis and inflammation through down regulation of autophagy mediated by Akt signaling pathway.

Antithrombin III Alleviates Myocardial Ischemia/Reperfusion Injury by Inhibiting Excessive Autophagy in a Phosphoinositide 3-Kinase/Akt-Dependent Manner.

Autophagy is fundamental to myocardial ischemia/reperfusion (I/R) injury. Antithrombin III (AT) has been shown to protect cardiomyocytes against I/R injury; however, it is unknown whether it modulates autophagy. The objective of this study was to investigate whether AT regulates autophagy during I/R injury and, if so, to identify the potential mechanism involved. Our study showed that AT attenuated I/R injury in vivo and hypoxia/reoxygenation (H/R) injury in vitro. Autophagy was increased both in H9C2 cardiomyocytes during H/R injury and in mouse hearts following I/R injury. The stimulation of autophagy by rapamycin attenuated the protective effect of AT against H9C2 cell injury, indicating that autophagy is involved in the protective role of AT. Furthermore, the cardioprotective effects of AT were abolished by A6730, a specific Akt inhibitor. This study shows that AT exhibits cardioprotective effects by modulating autophagy during I/R injury in a phosphoinositide 3-kinase/Akt-dependent manner.

The safety of catheter ablation for premature ventricular contractions in patients without structural heart disease.

BACKGROUND: Patients with frequent premature ventricular contractions (PVCs) are often symptomatic. Catheter ablation was usually indicated to eliminate symptoms in patients with PVCs-induced cardiomyopathy. Currently, PVCs-ablation is also applied for patients with PVCs and no structural heart diseases (SHD); however, the safety and efficacy of ablation in these patients remains unclear. METHODS: In this retrospective study, data from patients who underwent ablation for PVCs from January 2010 to December 2016 at our hospital was retrieved. Predictors of complications and acute procedural success were evaluated. RESULTS: A total of 1231 patients (mean age 47.8 ± 16.8 years, 59% female) were included. The overall complication rate was 2.7%, and the most common complication was hydropericardium. Two ablation-related mortalities occurred. One patient died of coronary artery injury during the procedure and the other died from infectious endocarditis. Location (left ventricle and epicardium) was the main predictor of complications, with right ventricular outflow tract (RVOT) predicting fewer complications. The acute procedural success rate was 94.1% in all patients. The main predictor of acute procedural success was RVOT origin, while an epicardial origin was a predictor of procedural failure. CONCLUSION: Locations of left ventricle and epicardium were predictors of procedural complications for patients with PVCs. Therefore, ablation is not recommended in these patients. For other origins of PVCs, particularly RVOT origin, ablation is a safety and effective treatment.

Common and distinctive electrocardiographic characteristics and effective catheter ablation of idiopathic ventricular arrhythmias originating from different areas of ventricular septum adjacent to atrioventricular annulus.

OBJECTIVE: To investigate electrocardiographic (ECG) characteristics and radiofrequency catheter ablation (RFCA) efficacy for premature ventricular complexes (PVCs) and idiopathic ventricular tachycardias (IVTs) originating from ventricular septum areas adjacent to atrioventricular annulus (VS-AVA). METHODS: Among 1,505 consecutive PVCs/IVTs cases, 106 (7.04%) were confirmed as origin of VS-AVA guided by both fluoroscopy and three-dimensional mapping system during RFCA. Characteristics of surface 12-lead ECG were analyzed. RESULTS: The overall success rate for RFCA of PVCs/IVTs originating from VS-AVA was 82.08% (87/106), common ECG characteristics were: mainly positive R wave on lead I; dominant-positive R on aVL (91/106, 85.85%) for most, r (1/106, 0.94%) or qr (14/106, 13.21%) in few; QS or qs on aVR; and decreasing R wave amplitude and increasing S wave depth on II, III, and aVF from superior to inferior septum; and S wave on at least one inferior lead (generally III). Distinctive ECG features were: precordial transition zone before or after V2 for septum adjacent to mitral (MA, 19/19, 100.0%) or tricuspid (TA, 74/87,85.05%) annulus origin; initial r wave and rS on V1 for superior septum near TA (above His bundle) origin (9/10, 90.0%) with no initial r wave for most other origins; and QS on V1 for mid-inferior septum near TA origin (73/77, 94.81%) and QR (Qr, qR or qr) on V1 for septum near MA origin (17/19, 89.47%). CONCLUSION: Distinctive ECG characteristics of PVCs/IVTs originating from VS-AVA aid in origin localization guiding effective RFCA.

Effects of macrophage migration inhibitory factor on cardiac reperfusion injury in mice with depression induced by constant-darkness.

RATIONALE: Depression is associated with coronary artery disease and increases adverse outcomes and mortality in patients with acute myocardial infarction, but the underlying pathophysiological mechanisms remain unclear. OBJECTIVE: To evaluate the effect of macrophage migration inhibitory factor (MIF) on cardiac ischemia-reperfusion (I/R) injury in mice with constant darkness-induced depression. METHODS AND RESULTS: Twenty C57BL/6 mice (8 weeks old, male) were randomly divided into 2 groups: one group was housed in a 12h light/dark cycle environment (LD) and the other in a constant darkness environment (DD). After 3 weeks, constant darkness-exposed (DD) mice displayed depression-like behavior as indicated by increased immobility in the forced swim test (FST) and lower sucrose preference rate. Western blotting revealed cardiac MIF expression was significantly lower in the DD mice than that in the LD mice. Next, 84 mice were randomly divided into 4 groups: LD sham group, LD I/R group, DD sham group, and DD I/R group. Following ischemia and reperfusion, mice in the DD I/R group had a larger infarct area and lower heart function index than mice in the LD I/R group (P < 0.05 for both). The cardiac pAMPK and pACC expression levels of the DD I/R group were also lower in the DD I/R group (P < 0.05). CONCLUSION: DD-induced depression might cause decreased expression of MIF in the heart, resulting in downregulation of MIF-AMPK signaling and a subsequent adverse outcome after a cardiac I/R injury.

Macrophage migration inhibitory factor promoter polymorphisms (-794 CATT5-8): Relationship with soluble MIF levels in coronary atherosclerotic disease subjects.

BACKGROUND: We analyzed the relationship of -794 CATT5-8 MIF polymorphisms with soluble MIF in Coronary Atherosclerotic Disease (CAD) patients. METHODS: A total of 256 patients selected, on which 186 normal-coronary and 70 Coronary artery disease subjects, were recruited in the study (Retrospectively registered). Genotyping of -794 CATT5-8 polymorphisms were performed by PCR and DNA sequencing. Serum MIF levels were measured using an ELISA kit. Patients were classified by coronary angiogram, and CAD based on Gensini's integral degree (angiographic scoring system). RESULTS: The allele frequency and genotype frequency of -794 CATT5-8 did not show any differences in normal-coronary subjects and CAD subjects. In CAD patients, serum MIF levels was lower in CATT (5) subjects than in CATT (7) subjects, while the genotype of -794 CATT5-8 did not show differences in serum MIF levels. In addition, we found a decrease in serum MIF levels in carriers of the (5/5) genotypes the -794 CATT5-8 MIF polymorphisms, although it was not significant. There was no relationship of CAD class and the allele frequency of -794 CATT5-8. CONCLUSIONS: This study found no association between CAD class and -794 CATT5-8 MIF polymorphisms with soluble MIF levels in CAD Subjects. TRIAL REGISTRATION: NCT01750502 (November 2012, Retrospectively registered).

Amifostine Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Apoptosis and Oxidative Stress.

The present study was aimed at investigating the effect of amifostine on myocardial ischemia/reperfusion (I/R) injury of mice and H9c2 cells cultured with TBHP (tert-butyl hydroperoxide). The results showed that pretreatment with amifostine significantly attenuated cell apoptosis and death, accompanied by decreased reactive oxygen species (ROS) production and lower mitochondrial potential (ΔΨm). In vivo, amifostine pretreatment alleviated I/R injury and decreased myocardial apoptosis and infarct area, which was paralleled by increased superoxide dismutase (SOD) and reduced malondialdehyde (MDA) in myocardial tissues, increased Bcl2 expression, decreased Bax expression, lower cleaved caspase-3 level, fewer TUNEL positive cells, and fewer DHE-positive cells in heart. Our results indicate that amifostine pretreatment has a protective effect against myocardial I/R injury via scavenging ROS.

Ox-LDL induces dysfunction of endothelial progenitor cells via activation of NF-κB.

Dyslipidemia increases the risks for atherosclerosis in part by impairing endothelial integrity. Endothelial progenitor cells (EPCs) are thought to contribute to endothelial recovery after arterial injury. Oxidized low-density lipoprotein (ox-LDL) can induce EPC dysfunction, but the underlying mechanism is not well understood. Human EPCs were cultured in endothelial growth medium supplemented with VEGF (10 ng/mL) and bFGF (10 ng/mL). The cells were treated with ox-LDL (50 µg/mL). EPC proliferation was assayed by using CCK8 kits. Expression and translocation of nuclear factor-kabba B (NF-κB) were evaluated. The level of reactive oxygen species (ROS) in cells was measured using H2DCF-DA as a fluorescence probe. The activity of NADPH oxidase activity was determined by colorimetric assay. Ox-LDL significantly decreased the proliferation, migration, and adhesion capacity of EPCs, while significantly increased ROS production and NADPH oxidase expression. Ox-LDL induced NF-κB P65 mRNA expression and translocation in EPCs. Thus ox-LDL can induce EPC dysfunction at least by increasing expression and translocation of NF-κB P65 and NADPH oxidase activity, which represents a new mechanism of lipidemia-induced vascular injury.

bFGF regulates autophagy and ubiquitinated protein accumulation induced by myocardial ischemia/reperfusion via the activation of the PI3K/Akt/mTOR pathway.

Autophagy is involved in the development and/or progression of many diseases, including myocardial ischemia/reperfusion (I/R). In this study, we hypothesized a protective role of basic fibroblast growth factor (bFGF) both in vivo and in vitro and demonstrated that excessive autophagy and ubiquitinated protein accumulation is involved in the myocardial I/R model. Our results showed that bFGF improved heart function recovery and increased the survival of cardiomyocytes in myocardial I/R model. The protective effect of bFGF is related to the inhibition of LC3II levels. Additionally, bFGF enhances the clearance of Ub by p62 and increases the survival of H9C2 cells. Moreover, silencing of p62 partially blocks the clearance of Ub and abolishes the anti-apoptosis effect of bFGF. An shRNA against the autophagic machinery Atg7 increased the survival of H9C2 cells co-treated with bFGF and rapamycin. bFGF activates the downstream signaling of the PI3K/Akt/mTOR pathway. These results indicate that the role of bFGF in myocardial I/R recovery is related to the inhibition of excessive autophagy and increased ubiquitinated protein clearance via the activation of PI3K/Akt/mTOR signaling. Overall, our study suggests a new direction for bFGF drug development for heart disease and identifies protein signaling pathways involved in bFGF action.

Factors associated with decision time for patients with ST-segment elevation acute myocardial infarction.

Increased delay in visiting a hospital for patients with ST-segment elevation myocardial infarction (STEMI) is often associated with poor outcomes. The factors associated with the decision time were analyzed by comparing the characteristics of patients with delays longer or shorter than the median of 60 min. Pre-hospital delay tended to be longer for patients living in suburban areas compared to those in urban areas (P=0.015). Shorter decision time was more likely among older patients. Being married, medical insurance coverage, and the level of educational qualification did not affect decision time. More efforts should be paid to educate the patients with high risk in suburban areas in order to effectively reduce pre-hospital delays.

Shengmai injection, a traditional chinese patent medicine, for intradialytic hypotension: a systematic review and meta-analysis.

Intradialytic hypotension (IDH) is a global public health problem. A rising number of IDH sufferers resort to Chinese patent medicine, Shengmai Injection (SMI) in China. The objectives of present study are to assess the effectiveness and safety of SMI as an adjunct therapy for IDH. A systematic search of 6 medical databases was performed up to December 2011. Randomized trials involving SMI adjuvant therapy versus conventional therapy were identified. RevMan 5.0 was used for data analysis. Ten randomized clinical trials with 437 participants were identified. Methodological quality was considered inadequate in all trials. Compared with conventional therapy, SMI adjunct therapy showed significant effects in improving the clinic effective rate (P < 0.01), decreasing the incidence of IDH episode (P < 0.01), decreasing the frequency of nursing interventions (P < 0.01), and increasing diastolic blood pressure (P < 0.01). There was no statistical significance in the improvement of mean arterial pressure (P = 0.22) and systolic blood pressure (P = 0.08) between two groups. Four studies had mentioned adverse events, but no serious adverse effects were reported in any of the included trials. In conclusion, SMI adjunct therapy appears to be potentially effective in treatment of IDH and is generally safe. However, further rigorous designed trials are needed.

Catheter ablation of idiopathic ventricular arrhythmias originating from left ventricular epicardium adjacent to the transitional area from the great cardiac vein to the anterior interventricular vein.

OBJECTIVES: This study aimed to investigate electrocardiographic characteristics and effects of radiofrequency catheter ablation (RFCA) for patients with symptomatic premature ventricular complexes (PVCs) and idiopathic ventricular tachycardias (IVTs), originating from the different portions of the left coronary veins. BACKGROUND: Inadequate distinction was made in the past for the PVC/IVTs located in the different portions of the left coronary veins, especially the distal great cardiac vein (DGCV) and the proximal portion of the anterior interventricular vein (PAIV) and the extended tributary of DGCV located distal to the origin of AIV (EDGCV). METHODS: Characteristics of body surface electrocardiogram (ECG) and electrophysiologic recordings were analyzed in 12 patients with symptomatic PVCs/IVTs originating from the vicinity of the left coronary veins. RESULTS: Among 490 patients with PVCs/IVTs, the incidence of ventricular arrhythmias originating from the left ventricular epicardium adjacent to the transitional area from the GCV to the AIV was 2.45%. Four had PVCs/IVTs from DGCV, 5 from PAIV, and 3 from EDGCV. There were different characteristics of ECG of PVCs/VT originating from the DGCV and PAIV and EDGCV. Successful RFCA in all 12 patients could be achieved (100% acute procedural success). No complications were observed. During a median follow up of 17 months (range 6-45 months), 2 had recurrent ventricular arrhythmia (recurrence rate: 16.67%). CONCLUSIONS: ECG characteristics of PVCs/VTs originating from the different portions of the left coronary veins (DGCV and PAIV and EDGCV) are different, and can help regionalize the origin of these arrhythmias. RFCA within the coronary venous system was relatively effective and safe for the PVCs/IVTs and should be seen as an alternative approach, when the left-sided PVCs/IVTs could not be eliminated by RFCA from the endocardium or aortic sinus of Valsalva.