Atrial Septostomy for Left Atrial Decompression During Extracorporeal Membrane Oxygenation by Inoue Balloon Catheter.

BACKGROUND: Refractory pulmonary edema is an infrequent but serious complication in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) for myocardial failure. Left atrial (LA) decompression in this setting is important. Although a few methods have been reported, the experience is mostly limited to children. We aimed to evaluate the feasibility of Inoue balloon catheter in percutaneous trans-septal LA decompression in adult cardiogenic patients.Methods and Results:We retrospectively analyzed 16 procedures of trans-septal LA decompression by Inoue balloon catheter in 15 VA-ECMO patients (aged 22-65 years, 6 men) with refractory pulmonary edema from May 2012 to December 2014. Mean left ventricular ejection fraction was 15%. The cause of cardiogenic shock included 7 cases of ischemic heart disease, 1 of dilated cardiomyopathy, 5 of myocarditis, and 2 of fatal ventricular arrhythmia.The procedures were performed 4.3 days after ECMO. Inoue balloon size was 24-27 mm. LA septostomy were successfully created in 14 patients. Procedure time on average was 36.8 min (range, 15-85 min). There were no procedure-related complications.Radiography on the next day showed rapid resolution of pulmonary edema. CONCLUSIONS: Trans-septal LA decompression by Inoue balloon catheter is a feasible alternative method for adult patients with refractory pulmonary edema under ECMO.

Clinical Outcomes of Polytetrafluoroethylene-Covered Stents for Coronary Artery Perforation in Elderly Patients Undergoing Percutaneous Coronary Interventions.

BACKGROUND: Coronary artery perforation (CAP) during percutaneous coronary intervention (PCI) is associated with increased mortality. Polytetrafluoroethylene covered stents (CS) are an effective approach to treat CAP, but data regarding elderly patients requiring CS implantation for CAP are limited. The aim of this study is to report clinical data for elderly CAP patients undergoing CS implantation during PCI. METHODS: Nineteen consecutive elderly patients (≥ 65 years) undergoing CS implantation due to PCI-induced CAP in a tertiary referral center from July 2003 to April 2016 were retrospectively examined. RESULTS: There were 13 men and six women, with a mean age of 75.3 ± 5.6 years (range: 65-86 years). Perforation grade was Ellis type II in five patients (26.3%), and Ellis type III in 14 patients (73.7%). Cardiac tamponade developed in six patients (31.6%), and intra-aortic balloon pumping was needed in four patients (21.1%). The overall success rate for CS implantation rate was 94.7%. The overall in-hospital mortality rate was 15.8%; the in-hospital myocardial infarction rate was 63.2%. Among 16 survival-to-discharge cases, dual antiplatelet therapy (DAPT) was prescribed in 14 cases (87.5%) for a mean duration of 14 months. Overall, there were five angiogram- proven CS failures among 18 patients receiving successful CS implantation. The 1, 2 and 4 years of actuarial freedom from the CS failure were 78%, 65%, and 43% in the angiogram follow-up patients. CONCLUSIONS: CS implantation for CAP is feasible and effective in elderly patients, while CS failure remains a major concern that encourages regular angiographic follow-up in these case.

MicroRNA-146a decreases high glucose/thrombin-induced endothelial inflammation by inhibiting NAPDH oxidase 4 expression.

Diabetes is associated with hyperglycemia and increased thrombin production. However, it is unknown whether a combination of high glucose and thrombin can modulate the expression of NAPDH oxidase (Nox) subtypes in human aortic endothelial cells (HAECs). Moreover, we investigated the role of a diabetes-associated microRNA (miR-146a) in a diabetic atherothrombosis model. We showed that high glucose (HG) exerted a synergistic effect with thrombin to induce a 10.69-fold increase in Nox4 mRNA level in HAECs. Increased Nox4 mRNA expression was associated with increased Nox4 protein expression and ROS production. Inflammatory cytokine kit identified that the treatment increased IL-8 and IL-6 levels. Moreover, HG/thrombin treatment caused an 11.43-fold increase of THP-1 adhesion to HAECs. In silico analysis identified the homology between miR-146a and the 3'-untranslated region of the Nox4 mRNA, and a luciferase reporter assay confirmed that the miR-146a mimic bound to this Nox4 regulatory region. Additionally, miR-146a expression was decreased to 58% of that in the control, indicating impaired feedback restraint of HG/thrombin-induced endothelial inflammation. In contrast, miR-146a mimic transfection attenuated HG/thrombin-induced upregulation of Nox4 expression, ROS generation, and inflammatory phenotypes. In conclusion, miR-146a is involved in the regulation of endothelial inflammation via modulation of Nox4 expression in a diabetic atherothrombosis model.

Angiotensin-(1-7) decreases glycated albumin-induced endothelial interleukin-6 expression via modulation of miR-146a.

The presence of glycated albumin (GA) is associated with increased diabetic complications. This study investigated the effect of angiotensin-(1-7) on the expression of GA-induced endothelial interleukin-6 (IL-6) in human aortic endothelial cells (HAECs). We also evaluated whether miR-146a is involved in the post-transcriptional regulation of angiotensin-(1-7). HAECs were stimulated with GA with or without angiotensin-(1-7) pretreatment. Inflammatory cytokine screening approach identified that angiotensin-(1-7) (10(-7) M) potently inhibited GA (200 µg/mL)-stimulated endothelial IL-6 expression in conditioned medium. ELISA confirmed this finding. Real-time PCR showed that angiotensin-(1-7) decreased GA-induced intracellular IL-6 mRNA expression and western blotting showed that angiotensin-(1-7) decreased GA-induced intracellular IL-6 protein expression. Bioinformatics' miR target analysis identified homology between miR-146a and the 3'-UTR of the human IL-6 mRNA, suggesting a potential regulation of IL-6 by miR-146a. Treatment with GA decreased endothelial miR-146a expression to 37.2% of the albumin control, while angiotensin-(1-7) increased endothelial miR-146a expression to 1.9-times that of the medium control. Pretreatment with angiotensin-(1-7) inhibited the GA-mediated downregulation of miR-146a to 78.9% of the albumin control levels. Furthermore, the inhibitory effect of angiotensin-(1-7) on IL-6 expression was abolished in GA-treated, miR-146a inhibitor-transfected HAECs. In conclusion, these results suggest that angiotensin-(1-7) exerted an endothelial protective effect through IL-6 downregulation, and miR-146a modulation is involved in this protective effect.

Prognostic significance of reciprocal ST-segment depression in patients with acute STEMI undergoing immediate invasive intervention.

PURPOSES: Reciprocal changes are frequent in patients with acute ST-segment elevation myocardial infarction (STEMI). However, their prognostic significance is not clear in patients undergoing immediate invasive intervention. BASIC PROCEDURE: We retrospectively examined 165 consecutive patients with STEMI receiving immediate invasive intervention. The first electrocardiography taken in the emergency department was analyzed. Patients were assigned to 2 groups: with a reciprocal change (group I, n = 100) and without a reciprocal change (group II, n = 65). MAIN FINDINGS: Electrocardiographs revealed that more anterolateral and inferior STEMI occurred in group I and more anterior STEMI occurred in group II. In the emergency department, group I had lower systolic and diastolic blood pressures, higher ventricular tachycardia and fibrillation rates, and higher cardiopulmonary resuscitation rates than did group II. Upon admission, peak troponin I levels were significantly higher in group I, and more group I patients required intra-aortic balloon pumping support. This unstable hemodynamic condition in group I patients was reflected by their higher in-hospital mortality rate. Multivariate analysis showed that age (odds ratio [OR], 1.103; 95% confidence interval [CI], 1.022-1.190; P = .012), Killip class (OR, 2.785; 95% CI, 1.049-7.400; P = .040), and reciprocal change (OR, 9.553; 95% CI, 1.146-79.608; P = .037) remained as independent predictors of in-hospital mortality. Actuarial freedom from all-cause mortality was worse in group I (P = .046). PRINCIPAL CONCLUSIONS: The data suggest that patients with STEMI with reciprocal electrocardiographic changes have unstable hemodynamic status and poorer outcomes. Further prospective studies using a larger patient population are needed.

(-)-Epigallocatechin-3-gallate decreases thrombin/paclitaxel-induced endothelial tissue factor expression via the inhibition of c-Jun terminal NH2 kinase phosphorylation.

Patients with paclitaxel-eluting stents are concerned with stent thrombosis caused by premature discontinuation of dual antiplatelet therapy or clopidogrel resistance. This study investigates the effect of (-)-epigallocatechin-3-gallate (EGCG) on the expression of thrombin/paclitaxel-induced endothelial tissue factor (TF) expressions in human aortic endothelial cells (HAECs). EGCG was nontoxic to HAECs at 6h up to a concentration of 25 micromol/L. At a concentration of 25 micromol/L, EGCG pretreatment potently inhibited both thrombin-stimulated and thrombin/paclitaxel-stimulated endothelial TF protein expression. Thrombin and thrombin/paclitaxel-induced 2.6-fold and 2.9-fold increases in TF activity compared with the control. EGCG pretreatment caused a 29% and 38% decrease in TF activity on thrombin and thrombin/paclitaxel treatment, respectively. Real-time polymerase chain reaction (PCR) showed that thrombin and thrombin/paclitaxel-induced 3.0-fold and 4.6-fold TF mRNA expressions compared with the control. EGCG pretreatment caused an 82% and 72% decrease in TF mRNA expression on thrombin and thrombin/paclitaxel treatment, respectively. The c-Jun terminal NH2 kinase (JNK) inhibitor SP600125 reduced thrombin/paclitaxel-induced TF expression. Furthermore, EGCG significantly inhibited the phosphorylation of JNK to 49% of thrombin/paclitaxel-stimulated HAECs at 60min. Immunofluorescence assay did not show an inhibitory effect of EGCG on P65 NF-kappaB nuclear translocation in the thrombin/paclitaxel-stimulated endothelial cells. In conclusion, EGCG can inhibit TF expression in thrombin/paclitaxel-stimulated endothelial cells via the inhibition of JNK phosphorylation. The unique property of EGCG may be used to develop a new drug-eluting stent by co-coating EGCG and paclitaxel.

Hispolon promotes MDM2 downregulation through chaperone-mediated autophagy.

Amplification and overexpression of murine double minute (MDM2) has been observed in several human cancers. Some chemotherapeutic agents cause MDM2 ubiquitination and degradation in a proteasome-dependent system. In addition to the proteasome system, chaperone-mediated autophagy (CMA) is a lysosomal pathway for selective misfolded protein degradation. Molecular chaperone heat shock cognate 70 protein (Hsc70) recognizes the misfolded proteins, which are then delivered to lysosome-associated membrane protein type 2A (LAMP2A) for lysosomal degradation. Our previous study reported that hispolon was able to induce cell apoptosis and downregulate MDM2 expression. In this study, our results showed that the proteasome inhibitor, MG132, could not inhibit hispolon-induced MDM2 downregulation. In contrast, both inhibition of lysosomes with NH(4)Cl and inhibition of LAMP2A using siRNA partially attenuated hispolon-induced MDM2 downregulation. To determine whether Hsc70 recognizes MDM2 on amino acids 135-141, SMP14 antibody was used to compete with Hsc70 for interaction with MDM2. After Hsc70 knockdown, SMP14 antibody immunoprecipitated increased MDM2. We also found that hispolon induced increased association of Hsp70, Hsc70, Hsp90 and LAMP2A with MDM2. This association was inhibited in cells pretreated with geldanamycin (GA), an Hsp90 inhibitor. GA also attenuated hispolon-induced MDM2 downregulation. Meanwhile, inhibition of Hsc70 using siRNA attenuated hispolon-induced MDM2 downregulation. Our study provides the first example of the ability of hispolon to mediate MDM2 downregulation in lysosomes through the CMA pathway.

Non-canonical Interaction Between O-Linked N-Acetylglucosamine Transferase and miR-146a-5p Aggravates High Glucose-Induced Endothelial Inflammation.

Background and Aims: Increased O-GlcNAc transferase (OGT)-induced O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification is linked with diabetic complications. MicroRNA-146a-5p (miR-146a-5p) is a negative inflammatory regulator and is downregulated in diabetes. Here, we investigated the interaction between miR-146a-5p and OGT. Methods: Human aortic endothelial cells (HAECs) were stimulated with high glucose (25 mM) and glucosamine (25 mM) for 24 h. Western blot, real time PCR, bioinformatics analysis, luciferase reporter assay, miR-146a-5p mimic/inhibitor transfection, siRNA OGT transfection, miR-200a/200b mimic transfection, and OGT pharmacological inhibition (ST045849) were performed. The aorta from miR-146a-5p mimic-treated db/db mice were examined by immunohistochemistry staining. Results: HG and glucosamine upregulated OGT mRNA and protein expression, protein O-GlcNAcylation, and IL-6 mRNA and protein expression. Real time PCR analysis found that miR-146a-5p was decreased in HG- and glucosamine-stimulated HAECs. This suggested that OGT-induced protein O-GlcNAcylation as a mechanism to downregulate miR-146a-5p. Bioinformatic miR target analysis excluded miR-146a-5p as a post-transcriptional regulator of OGT. However, a luciferase reporter assay confirmed that miR-146a-5p mimic bound to 3'-UTR of human OGT mRNA, indicating that OGT is a non-canonical target of miR-146a-5p. Transfection with miR-146a-5p mimic and inhibitor confirmed that miR-146a-5p regulated OGT/protein O-GlcNAcylation/IL-6 expression levels. Furthermore, OGT siRNA transfection, miR-200a/miR-200b mimic transfection, and ST045849 increased HG-induced miR-146a-5p expression levels, indicating that HG-induced miR-146a-5p downregulation is partially mediated through OGT-mediated protein O-GlcNAcylation. In vivo, intravenous injections of miR-146a mimic decreased endothelial OGT and IL6 expression in db/db mice. Conclusion: A non-canonical positive feedback interaction between miR-146a-5p and OGT is involved in a vicious cycle to aggravate HG-induced vascular complications.

Paclitaxel induces up-regulation of tissue factor in human aortic endothelial cells.

Patients who underwent paclitaxel-eluting stent implantation are at a risk of developing late stent thrombosis. However, it is unclear whether paclitaxel alone can modulate tissue factor (TF) expression in human aortic endothelial cells (HAEC). HAEC were stimulated with paclitaxel. Western blotting, real-time PCR, and a chromogenic TF activity assay were done. In HAEC, while paclitaxel (10 (-5) mol/L to 10 (-9) mol/L) treatment for 5 h up-regulated the expression of TF in a dose-dependent manner, paclitaxel cotreatment with thrombin further enhanced it. While paclitaxel (10 (-5) mol/L) itself induced a 3.7-fold enhancement in TF activity, its cotreatment along with thrombin elicited a 7.6-fold increase in TF activity. Paclitaxel also caused an 8.1-fold increase in TF mRNA expression, and paclitaxel cotreatment with thrombin caused a 13.6-fold enhancement in TF mRNA expression. In summary, paclitaxel alone can up-regulate endothelial TF expression. These findings are significant for the patients receiving paclitaxel-eluting stents, and they may provide opportunities to develop novel therapeutic strategies for DES thrombosis.

Corrigendum: MicroRNA-200a/200b Modulate High Glucose-Induced Endothelial Inflammation by Targeting O-linked N-Acetylglucosamine Transferase Expression.

[This corrects the article on p. 355 in vol. 9, PMID: 29720943.].

MicroRNA-200a/200b Modulate High Glucose-Induced Endothelial Inflammation by Targeting O-linked N-Acetylglucosamine Transferase Expression.

Background and Aims: Increased O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins by O-GlcNAc transferase (OGT) is associated with diabetic complications. Furthermore, oxidative stress promotes endothelial inflammation during diabetes. A previous study reported that microRNA-200 (miR-200) family members are sensitive to oxidative stress. In this study, we examined whether miR-200a and miR-200b regulate high-glucose (HG)-induced OGT expression in human aortic endothelial cells (HAECs) and whether miRNA-200a/200b downregulate OGT expression to control HG-induced endothelial inflammation. Methods: HAECs were stimulated with high glucose (25 mM) for 12 and 24 h. Real-time polymerase chain reaction (PCR), western blotting, THP-1 adhesion assay, bioinformatics predication, transfection of miR-200a/200b mimic or inhibitor, luciferase reporter assay, and transfection of siRNA OGT were performed. The aortic endothelium of db/db diabetic mice was evaluated by immunohistochemistry staining. Results: HG upregulated OGT mRNA and protein expression and protein O-GlcNAcylation levels (RL2 antibody) in HAECs, and showed increased intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin gene expression; ICAM-1 expression; and THP-1 adhesion. Bioinformatics analysis revealed homologous sequences between members of the miR-200 family and the 3'-untranslated region (3'-UTR) of OGT mRNA, and real-time PCR analysis confirmed that members of miR-200 family were significantly decreased in HG-stimulated HAECs. This suggests the presence of an impaired feedback restraint on HG-induced endothelial protein O-GlcNAcylation levels because of OGT upregulation. A luciferase reporter assay demonstrated that miR-200a/200b mimics bind to the 3'-UTR of OGT mRNA. Transfection with miR-200a/200b mimics significantly inhibited HG-induced OGT mRNA expression, OGT protein expression; protein O-GlcNAcylation levels; ICAM-1, VCAM-1, and E-selectin gene expression; ICAM-1 expression; and THP-1 adhesion. Additionally, siRNA-mediated OGT depletion reduced HG-induced protein O-GlcNAcylation; ICAM-1, VCAM-1, and E-selectin gene expression; ICAM-1 expression; and THP-1 adhesion, confirming that HG-induced endothelial inflammation is partially mediated via OGT-induced protein O-GlcNAcylation. These results were validated in vivo: tail-vein injection of miR-200a/200b mimics downregulated endothelial OGT and ICAM-1 expression in db/db mice. Conclusion: miR-200a/200b are involved in modulating HG-induced endothelial inflammation by regulating OGT-mediated protein O-GlcNAcylation, suggesting the therapeutic role of miR-200a/200b on vascular complications in diabetes.

Identification of Basic Fibroblast Growth Factor as the Dominant Protector of Laminar Shear Medium from the Modified Shear Device in Tumor Necrosis Factor-α Induced Endothelial Dysfunction.

Background and Aims: Endothelial dysfunction is a hallmark of cardiovascular diseases. The straight region of an artery is protected from atherosclerosis via its laminar blood flow and high shear stress. This study investigated the cytoprotective effects of a new laminar shear medium (LSM) derived from a modified cone-and-plate shear device and identified basic fibroblast growth factor (bFGF) secreted by human aortic endothelial cells (HAECs) as the dominant protective factor in the LSM. Methods: Based on a modified cone-and-plate shear device system, HAECs were exposed to laminar shear (15 dynes/cm2) and static control for 24 h to produce a new supernatant LSM and static medium (SM). Evaluation of the protective effects of LSM and SM on endothelial dysfunction induced by tumor necrosis factor (TNF)-α (10 ng/mL), which leads to production of reactive oxygen species (ROS), inflammatory monocyte adhesion, and tissue factor activity. ROS induction-, inflammation-, and thrombosis-related genes and protein expression were evaluated by quantitative-PCR and western blotting. To identify the cytokines that played a key role in the cytoprotective action of the LSM, we used cytokine antibody arrays, selected an abundant marker cytokine, bFGF, and validated the different cytoprotective effects of recombinant bFGF (rbFGF) and neutralization by monoclonal antibody (rbFGF+Ab) co-treatment. Aortic and lung tissues from different groups of C57BL/6J mice were examined by immunohistochemistry. SB203580 (specific inhibitor of p38) and BIX02189 (specific inhibitor of MEK5) were used to identify bFGF as the main cytoprotective factor acting via p38/MAPK and MEK5-KLF2 pathways. Results: Compared with traditional LSM, the new LSM not only significantly decreased TNF-α-induced intracellular adhesion molecule 1 and plasminogen activator inhibitor type 1 gene expression, but also significantly increased heme oxygenase 1 gene expression. The new LSM and bFGF attenuated TNF-α-induced ROS induction, inflammation, and tissue factor activity and inhibited the inflammatory- and thrombosis-related gene/protein overexpression both in vitro and in vivo. Mechanistically, the cytoprotective action of bFGF was mediated via the p38/MAPK and MEK5-KLF2 pathways. Conclusion: bFGF was identified as the critical factor mediating the cytoprotective effects of LSM derived from the modified laminar shear system.

MicroRNA-146a-5p Mediates High Glucose-Induced Endothelial Inflammation via Targeting Interleukin-1 Receptor-Associated Kinase 1 Expression.

Background and Aims: Interleukin-1 receptor-associated kinase-1 (IRAK-1) is critical for mediating toll-like receptor and interleukin-1 receptor signaling. In this study, we have examined whether IRAK-1 expression is altered in high glucose (HG)-stimulated human aortic endothelial cells (HAECs), and whether microRNAs (miRs) target IRAK-1 to regulate HG-induced endothelial inflammation. Methods: HAECs were treated with HG for 24 and 48 h. Real-time PCR, Western blot, monocyte adhesion assay, bioinformatics analysis, TaqMan® arrays, microRNA mimic or inhibitor transfection, luciferase reporter assay and siRNA IRAK-1 transfection were performed. The aortic tissues from db/db type 2 diabetic mice were examined by immunohistochemistry staining. Results: HG time-dependently increased IRAK-1 mRNA and protein levels in HAECs, and was associated with increased VCAM-1/ICAM-1 gene expression and monocyte adhesion. Bioinformatic analysis, TaqMan® arrays, and real-time PCR were used to confirm that miR-146a-5p, miR-339-5p, and miR-874-3p were significantly downregulated in HG-stimulated HAECs, suggesting impaired feedback restraints on HG-induced endothelial inflammation via IRAK-1. However, only miR-146a-5p mimic transfection reduced the HG-induced upregulation of IRAK-1 expression, VCAM-1/ICAM-1 expression, and monocyte adhesion. Additionally, IRAK-1 depletion reduced HG-induced VCAM-1/ICAM-1 gene expression, and monocyte adhesion, indicating that HG-induced endothelial inflammation was mediated partially through IRAK-1. In vivo, intravenous injections of miR-146a-5p mimic prevented endothelial IRAK-1 and ICAM-1 expression in db/db mice. Conclusion: These results suggest that miR-146a-5p is involved in the regulation of HG-induced endothelial inflammation via modulation of IRAK-1; indicating that miR-146a-5p may be a novel target for the treatment of diabetic vascular complications.

Angiotensin-(1-7) Inhibits Thrombin-Induced Endothelial Phenotypic Changes and Reactive Oxygen Species Production via NADPH Oxidase 5 Downregulation.

Background and Aims: The angiotensin-(1-7)/angiotensin-converting enzyme 2/Mas receptor axis counter-regulates the detrimental effects of angiotensin II. Beneficial effects of angiotensin-(1-7), including anti-inflammation, oxidative stress reduction, and anti-thrombosis, have been reported. Previous studies documented that ramipril decreased thrombin generation in human hypertension and that the anti-thrombotic effects of captopril and losartan were angiotensin-(1-7)-dependent, suggesting an interaction between thrombin and angiotensin-(1-7). However, it is not clear whether angiotensin-(1-7) can alleviate the endothelial phenotypic changes induced by thrombin. We have previously documented cytoskeleton remodeling, cell adhesion, and cell migration as dominant altered phenotypes in thrombin-stimulated human aortic endothelial cells (HAECs). In this study, we investigated whether angiotensin-(1-7) can modulate thrombin-induced phenotypic changes. Furthermore, we investigated whether NAPDH oxidase 5 (Nox5)-produced reactive oxygen species (ROS) play a significant role in angiotensin-(1-7)-mediated phenotypic changes. Methods: HAECs were pretreated with 100 nM angiotensin-(1-7) for 1 h, followed by stimulation with 2 units/mL thrombin for different times. Immunofluorescent assay, monocyte adhesion assay, wound-healing assay, ROS assay, real-time PCR, Western blotting, and Nox5 siRNA transfection were conducted. HAECs were pretreated with the ROS scavenger N-acetylcysteine (NAC) to determine whether thrombin-induced phenotypic changes depended on ROS production. Results: Angiotensin-(1-7) prevented thrombin-induced actin cytoskeleton derangements, monocyte adhesion, and migratory impairment. Nox5 siRNA transfection confirmed that thrombin-induced Nox5 expression stimulated ROS production and increased HO-1/NQO-1/ICAM-1/VCAM-1 gene expression, all of which were decreased by angiotensin-(1-7). Phenotypic changes induced by thrombin were prevented by NAC pretreatment. Conclusion: Angiotensin-(1-7) prevents actin cytoskeleton derangement, monocyte adhesion, and migration impairment induced by thrombin via downregulation of ROS production. In addition, thrombin-induced Nox5 expression is involved in the production of ROS, and angiotensin-(1-7) decreases ROS through its inhibitory effect on Nox5 expression.

Percutaneous treatment of dysfunctional Brescia-Cimino fistulae through a radial arterial approach.

BACKGROUND: Dysfunctional Brescia-Cimino fistulae contribute to significant morbidity in hemodialysis patients. These fistulae normally are treated through a retrograde venous approach. There are no data regarding a transradial approach. Furthermore, measurement of pressure reduction in the radial artery appears to be useful. METHODS: We retrospectively examined 50 interventions to treat 49 patients (17 men, 32 women; mean age, 61.8 +/- 10.6 years) with Brescia-Cimino fistulae. Inclusion criteria were patients with palpable radial arteries and dysfunctional end-to-side Brescia-Cimino fistulae. Patients with infected fistulae, contrast allergy, upper-arm/synthetic graft/central-vein stenosis, and end-to-end Brescia-Cimino fistulae were excluded from the study. Radial arterial pressures before and after angioplasty were compared as a surrogate of stenosis relief. Anatomic and clinical success rates were calculated. RESULTS: Sixty-five stenoses and 4 total occlusions were treated through radial access. All radial punctures were successful, except in 1 patient. Most lesions were located in the cephalic vein (87%). Mean length of treated lesions was 4.1 +/- 2.8 cm. Mean pretreatment diameter of lesion stenoses was 76.7% +/- 12.1%. Mean posttreatment diameter stenosis was 22.6% +/- 8.2% (P < 0.001). Systolic, diastolic, and mean blood pressures recorded from the radial artery decreased from 130 +/- 40, 60 +/- 18, and 87 +/- 27 to 88 +/- 40, 43 +/- 18, and 60 +/- 26 mm Hg (P < 0.001, P < 0.001, and P < 0.001), respectively. The anatomic success rate of the transradial approach was 91.3%. The clinical success rate of the transradial approach was 96%. CONCLUSION: The transradial approach is a feasible and highly effective approach to treat dysfunctional Brescia-Cimino fistulae. Measuring blood pressure reduction through the radial artery appears promising as a hemodynamic evaluation method.

Pyogenic liver abscess in ESRD patients undergoing maintenance dialysis therapy.

BACKGROUND: Patients with end-stage renal disease (ESRD) on dialysis therapy have increased susceptibility to bacterial infection. Data regarding pyogenic liver abscess in this population are rare. METHODS: We retrospectively examined all cases of pyogenic liver abscess in patients undergoing maintenance dialysis therapy in 2 tertiary referral centers. Medical records of patients with ESRD with a pyogenic liver abscess from January 1995 to September 2004 were studied. RESULTS: Twenty-seven of 20,676 admitted patients with ESRD were found to have a pyogenic liver abscess. The major predisposing factor was diabetes mellitus (59.3%). The most common clinical symptoms were fever and chills (85.2%). A rare presentation of hiccup was noted in 2 peritoneal dialysis patients, and endophthalmitis was noted in 2 patients with liver abscess caused by Klebsiella pneumoniae. Abscesses were located mainly in the right lobe (70.4%) and presented as a solitary mass (74.1%). K pneumoniae was the most common bacteria isolated in blood cultures (51.9%) and liver abscess aspirates (37%). Invasive drainage approaches performed in 17 patients (63%) resulted in a unique complication of peritonitis in 4 peritoneal dialysis patients. The difference in mortality rates between patients who underwent invasive procedures and those who did not was not significant (P = 0.68). The overall in-hospital mortality rate of patients with ESRD with a pyogenic liver abscess was 33.3%. CONCLUSION: Although pyogenic liver abscess is uncommon in patients with ESRD undergoing maintenance dialysis therapy, it is still a disease of significant mortality.

Identification of Cofilin-1 Induces G0/G1 Arrest and Autophagy in Angiotensin-(1-7)-treated Human Aortic Endothelial Cells from iTRAQ Quantitative Proteomics.

The angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis is a pathway that acts against the detrimental effects of the renin-angiotensin system. However, the effects of angiotensin-(1-7) on endothelial protein expression and the related phenotypes are unclear. We performed a duplicate of iTRAQ quantitative proteomic analysis on human aortic endothelial cells (HAECs) treated with angiotensin-(1-7) for 6 hours. Cofilin-1 was identified as a highly abundant candidate with consistent >30% coverage and >1.2-fold overexpression in the angiotensin-(1-7)-treated group. Gene ontology analysis showed that the "regulation_of_mitosis" was significantly altered, and cell cycle analysis indicated that the 6-hour angiotensin-(1-7) treatment significantly induced G0/G1 arrest. Knockdown of the cofilin-1 (CFL1) gene suggested the G0/G1 phase arrest was mediated by the modulation of p27 and the p21/Cyclin/CDK complex by Cofilin-1. Interestingly, quiescent HAECs escaped G0/G1 arrest upon angiotensin-(1-7) treatment for 24 hours, and angiotensin-(1-7) induced autophagy by upregulating Beclin-1 and microtubule-associated protein 1 light chain 3b-II expression, which was also attenuated by A779 pre-treatment and CFL1 knockdown. After pre-treatment with 3-methyladenine (3MA), treatment with angiotensin-(1-7) for 24 h induced significant G0/G1 phase arrest and apoptosis, suggesting a pro-survival role of autophagy in this context. In conclusion, Cofilin-1 plays a dominant role in angiotensin-(1-7)-induced G0/G1 arrest and autophagy to maintain cellular homeostasis in HAECs.

iTRAQ quantitative proteomics-based identification of cell adhesion as a dominant phenotypic modulation in thrombin-stimulated human aortic endothelial cells.

INTRODUCTION: The phenotypic changes in thrombin-stimulated endothelial cells include alterations in permeability, cell shape, vasomotor tone, leukocyte trafficking, migration, proliferation, and angiogenesis. Previous studies regarding the pleotropic effects of thrombin on the endothelium used human umbilical vein endothelial cells (HUVECs)-cells derived from fetal tissue that does not exist in adults. Only a few groups have used screening approaches such as microarrays to profile the global effects of thrombin on endothelial cells. Moreover, the proteomic changes of thrombin-stimulated human aortic endothelial cells (HAECs) have not been elucidated. MATERIALS AND METHODS: HAECs were stimulated with 2 units/mL thrombin for 5h and their proteome was investigated using isobaric tags for the relative and absolute quantification (iTRAQ) and the MetaCore(TM) software. RESULTS: A total of 627 (experiment A) and 622 proteins (experiment B) were quantified in the duplicated iTRAQ analyses. MetaCore(TM) pathway analysis identified cell adhesion as a dominant phenotype in thrombin-stimulated HAECs. Replicated iTRAQ data revealed that "Cell adhesion_Chemokines and adhesion," "Cell adhesion_Histamine H1 receptor signaling in the interruption of cell barrier integrity," and "Cell adhesion_Integrin-mediated cell adhesion and migration" were among the top 10 statistically significant pathways. The cell adhesion phenotype was verified by increased THP-1 adhesion to thrombin-stimulated HAECs. In addition, the expression of ICAM-1, VCAM-1, and SELE was significantly upregulated in thrombin-stimulated HAECs. CONCLUSIONS: Several regulatory pathways are altered in thrombin-stimulated HAECs, with cell adhesion being the dominant altered phenotype. Our findings show the feasibility of the iTRAQ technique for evaluating cellular responses to acute stimulation.

Technical and prognostic outcomes of double-balloon pericardiotomy for large malignancy-related pericardial effusions.

OBJECTIVE: To investigate both the use of immediate or elective double-balloon pericardiotomy (DBP) in patients with a large amount of malignancy-related pericardial effusion, and the prognosis of this subgroup. DESIGN: Observational study after DBP intervention. SETTING: Tertiary referral center. PATIENTS AND INTERVENTIONS: Fifty patients with malignancy, mainly lung and breast cancer, who were admitted to our critical care unit with a large amount of pericardial effusion. All received echocardiographic-guided pericardiocentesis. Group 1 consisted of 12 patients (24%) who received immediate DBP, and group 2 consisted of 38 patients (76%) who received delayed DBP 2.5 +/- 1.7 days later (mean +/- SD) after emergency pericardiocentesis with pigtail catheter drainage. MEASUREMENTS: After the procedure, and at 1 month, 3 months, and 6 months, echocardiography and chest radiography were performed to check for pneumothorax, pericardial effusion reaccumulation, or the appearance of pleural effusion after pigtail catheter removal. MAIN RESULTS: The procedure was successful and without recurrence in 44 patients (88%). Procedural complications were fever in 4 patients (33%) and 10 patients (26%) in group 1 and group 2, respectively (p = 0.72), and mild pneumothorax in 2 patients (17%) and 1 patient (3%) in group 1 and group 2, respectively (p = 0.14). Fifty percent of the patients died within 4 months, while 25% survived to 11 months. High serum calcium, a low albumin/globulin ratio, and positive results on pericardial effusion cytology were poor prognostic factors for long-term survival. CONCLUSION: Both immediate and delayed DBP are a safe and effective method of relieving large pericardial effusions in patients with cancer. Successful DBP without recurrence of pericardial effusion was achieved in 88% of all patients. Survival was related to the extent of the disease.

Transesophageal echocardiographic diagnosis of intracardiac entrapment of a Swan-Ganz catheter in open heart operation.

A Swan-Ganz catheter entrapment by a suture in the right atrial wall during open heart operation is presented. The diagnosis of the suture entrapment of the Swan-Ganz catheter to the right atrial wall was established by direct observation of the specific movement pattern of the cardiac structures when manual traction was applied from outside by a transesophageal echocardiographic examination.