tbuckley/cabot-search huggingface dataset:
Abstract 10441: Development of <i>in vivo</i> Tissue-Engineered Vascular Grafts With an Ultra Small Diameter of 0.6 mm (MicroBiotubes)
Authors: Daizo Ishii, Jun-Ichiro Enmi, Hidehiro Iida, Tetsu Satow, Jun C Takahashi, Kaoru Kurisu, Yasuhide Nakayama
Journal: Circulation (2015)

Introduction and Hypothesis: Small-caliber arterial substitutes are needed for various revascularization procedures. Biotubes, in vivo tissue-engineered autologous tubular tissues, have high performance potential as a reliable aortic vascular graft with diameter of over several mm. This study challenged the development of micron-ordered caliber Biotubes (MicroBiotubes: MBs) with diameter of 0.6 mm and their quality and patency were non-invasively observed by optical coherence tomography (OCT) and magnetic resonance angiography (MRA), respectively. Methods: The mold for multiple preparing of MBs was assembled by several stainless wires covered with silicone tubes with outer diameter of 0.6 mm (Fig. 1A). The molds were surgically embedded into the dorsal subcutaneous pouches of rats. After 2 months, the molds were harvested with surrounding tissues and MBs were obtained, as encapsulated connective tissues, by removing the molds. MBs (length, 10 mm) after storing in 70% ethanol were allogenicaly implanted in rat femoral arteries (diameter, ca. 0.5 mm) by end-to-end anastomosis without use of any anticoagulant agents (Fig. 1B). Results: The OCT imaging showed homogeneous wall thickness without damage of MBs with a diameter of 0.6 mm. Patency at immediately after implantation was confirmed also by the imaging and at 1 month was by MRA (83.3%, n=6). Vascular structure with multi-layered elastic fiber and collagen fiber was constructed with endothelial cells and α-SMA-positive cells. The high patency was maintained for 6 months (Fig. 1C). Conclusions: The world’s smallest caliber vascular grafts with high patency and in situ regenerative activity were developed. The Biotubes could acquire high reliability for vascular grafts with diameter ranging from micrometer to centimeter.
Abstract 18092: Statin Use After an Acute In-Hospital Myocardial Infarction Among Medicare Beneficiaries
Authors: Huifeng Yun, Monika Safford, Todd Brown, Michael Farkouh, Shia Kent, Emily Levitan, Pradeep Sharma, Meredith Kilgore, Vera Bittner, Robert Rosenson, Paul Muntner
Journal: Circulation (2013)

Background: American Heart Association (AHA) guidelines recommend all patients are discharged on a statin following a coronary heart disease (CHD) event. Many patients have an acute myocardial infarction (AMI) while hospitalized for another reason but the use of statins upon discharge in this population has not been well studied. Methods: Using the Medicare 5% national random sample, we identified beneficiaries who had a hospital discharge diagnosis for AMI or who underwent coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) in 2007-2009. Medicare requires the primary diagnosis code to represent the initial reason for hospitalization; secondary discharge diagnosis codes capture complications including in-hospital AMI. Beneficiaries taking and not taking statins prior to their hospitalization were analyzed separately. Filling a statin prescription within 90 days after hospital discharge was identified using Medicare Part D claims. Results: Of 5,810 and 8,517 Medicare beneficiaries taking and not taking statins prior to their CHD-related hospitalization, 84% and 55% filled a statin within 90 days of discharge, respectively. The proportion of beneficiaries filling a statin following discharge was substantially lower among those with a secondary versus primary discharge diagnosis of AMI, or PCI or CABG (Table). After multivariable adjustment, beneficiaries with a secondary discharge diagnosis of AMI were 41% (risk ratio = 0.59, 95% CI: 0.54 - 0.65) and 11% (risk ratio = 0.89; 95% CI: 0.82 - 0.97) less likely to fill a statin compared to those with a primary discharge diagnosis of AMI. Conclusion: A high percentage of Medicare beneficiaries with in-hospital AMIs do not fill statins following hospital discharge. Reasons why patients with in-hospital AMIs do fill statins following discharge need to be identified.
Abstract 18065: The Upregulation of MicroRNA miR-21 Mediates Concentric Left Ventricle Remodeling in a Rat Model of Chronic Renocardiac Syndrome
Authors: Alison J Kriegel, Allen W Cowley, Mingyu Liang
Journal: Circulation (2013)

Chronic kidney disease (CKD) puts patients at a greatly increased risk of cardiovascular disease in a condition termed chronic renocardiac syndrome (RCS). We have utilized the 5/6 nephrectomy (5/6 NX) model in Sprague Dawley rats to study the gradual development of cardiac dysfunction resulting from declining kidney function. Previously, we identified alterations in several microRNAs (miRNAs) in left ventricle (LV) tissue 7 weeks after 5/6 NX surgery. We hypothesized that the upregulation of miR-21 in the LV following 5/6 NX contributes to LV pathology, rather than being a consequence of it. In situ hybridization revealed that miR-21 expression in the LV of 5/6 NX animals is highest in regions of perivascular fibrosis. To study the impact of miR-21 on LV remodeling and function, we delivered locked-nucleic acid (LNA) modified anti-miR-21 or anti-scrambled-miR (Exiqon, delivered i.v. at 1 mg/kg) to 5/6 NX animals (n=6/group) in 3 sequential days at 1 week post-surgery, and again 4 weeks post-surgery. Echocardiography was performed prior to 5/6 NX surgery and bi-weekly thereafter, throughout the 7 week study, to evaluate remodeling and function (anti-miR-21 vs. anti-scramble treated for all comparisons). The average LV miR-21 expression was reduced nearly 12-fold with anti-miR-21 treatment when measured 7 weeks post-5/6 NX. Anti-miR-21 treatment preserved stroke volume and fractional shortening between weeks 3 and 5 post-5/6 NX while both functional indices declined in anti-scramble treated rats. Additionally, concentric LV remodeling (LV wall hypertrophy and reduced chamber diameter) 5 weeks post-5/6 NX was completely prevented with anti-miR-21 treatment. At 7 weeks post-5/6 NX, when LV decompensation is evident in untreated rats, anti-miR-21 treatment maintained LV wall thickness and chamber diameter while fractional shortening was significantly increased (p &lt;0.05). Anti-miR-21 treatment had no effect on blood pressure. We conclude that chronic knockdown of miR-21 in the 5/6 NX model prevented pathological concentric remodeling. Together these data suggest that the upregulation of cardiac miR-21 following 5/6 NX is an important mediator of pathological cardiac remodeling and dysfunction.
Abstract 18031: Identification of Novel Determinants Towards Endothelial Differentiation Using a Heterokaryon Approach
Authors: Wing Tak Wong, Nazish Sayed, John P Cooke
Journal: Circulation (2013)

For directed differentiation of embryonic stem cells (ESCs) to endothelial cells (ECs), we need more information regarding the genes that are activated or suppressed, and their temporal order of activation, during EC specification. Accordingly, we sought to use heterokaryons (the stable fusion product of two different cell types) to identify critical determinants of EC differentiation. The premise is that cytoplasmic factors in the EC that maintain its phenotype will act on the ESC nucleus in the heterokaryon to reprogram it toward EC lineage. Using murine specific probes, or RNAseq, we will identify key genes that are modulated during early EC determination. Accordingly, we employed murine ESC labelled by transduction with retroviruses encoding GFP, and human ECs labelled with CellTracker Red, and induced heterokaryon formation using sendai virus-enveloped protein. Multi-nucleated heterokaryons were generated, which contained punctate murine nuclei and diffusely staining human nuclei. The dual-stained heterokaryons were sorted from the unfused cells and homokaryons by FACS. The extent and timing of differentiation of the murine ESCs within the heterokaryons were examined by probing for EC specific genes (KDR, CD144, vWF and CD31) and ES pluripotency markers (Nanog, Sox2 and Oct4) using murine specific primers. Intriguingly, heterokaryons appear to recapitulate ontogeny, in that early mesodermal genes (eg. KDR) are upregulated in murine ESC at 6h, whereas more EC-specific genes are not upregulated until later (eg. vWF at 24h). Data from RNAseq studies further confirmed the major transcriptional factors and regulators and identified some novel factors for endothelial differentiation. These novel genes will be confirmed using gain- and loss- of function studies of ESCs undergoing differentiation. These studies shall provide new knowledge regarding the hierarchy of genes regulating differentiation to the EC lineage and thus provide insight into vascular development, and ultimately new therapeutic avenues for vascular regeneration.
Abstract 17994: Rad Gtpase Depletion is a Novel Positive Inotrope Without Pathological Signaling
Authors: Janet R Manning, Guo Yin, Janos Magyar, Catherine Kaminski, Han-Zhong Feng, Gail Sievert, J.-P. Jin, Douglas Andres, Jonathan Satin
Journal: Circulation (2013)

Rationale: The small GTPase Rad is a negative regulator of voltage-dependent L-type calcium channel (LTCC) current (ICaL); however, the effects of Rad ablation on cardiomyocyte function and calcium homeostasis are unknown. Increased ICa,L may have dual effects , inducing transcriptional regulation in addition to positive inotropism. Alternatively, Rad as a member of the LTCC complex may restrict effects to contractile function only. Objective: This study tests the hypothesis that Rad-depletion causes positive inotropic effects without inducing pathological transcriptional signaling. Methods and Results: Ventricular myocytes from adult Rad-/- mice were isolated and evaluated for ICa,L and action potentials by patch clamp recordings, as well as calcium transients, and sarcomere shortening. Maximum ICaL is elevated in Rad-/-, decay kinetics are faster, and ICa,L activated at lower voltages thus mimicking effects of beta-adrenergic receptor (β-AR) stimulation. Diastolic and systolic calcium are elevated in Rad-/-, and sarcomere shortening is enhanced, particularly at lower pacing frequencies. Consequentially frequency-dependence of calcium transients is reduced in Rad-/-, and the frequency dependence of relaxation is also significantly blunted. In isolated ex vivo working hearts similar results were obtained, chiefly, contractility (+dP/dt) was elevated at baseline and was less responsive to acute β-AR stimulation. In single cells, at lower infra-physiological frequencies, non-stimulated CaMKII-sensitive calcium release is observed. Remarkably, Rad-/- hearts did not show pathological hypertrophic growth despite elevated levels of diastolic calcium. Conclusions: This study demonstrates that the depletion of Rad GTPase parallels β-AR agonism, remarkably without stimulating pathological cardiac hypertrophy. Thus, Rad GTPase is a novel potential therapeutic target for calcium homeostasis-driven positive inotropic support of the heart.
Abstract 11544: Rosuvastatin Dose-dependently Improves Flow-mediated Dilation, but Reduces Adiponectin Levels and Insulin Sensitivity in Hypercholesterolemic Patients
Authors: Kwang K Koh, Seung H Han, Pyung C Oh
Journal: Circulation (2016)

Background: Genetic analysis from patients participated in the randomized trials reported that the increased risk of type 2 diabetes noted with statins is at least partially explained by HMG-coenzyme A reductase inhibition. We investigated vascular and metabolic phenotypes of different dosages of rosuvastatin in hypercholesterolemic patients. Methods: This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. Forty-eight patients were given placebo, and 47, 48, and 47 patients given rosuvastatin 5,10, and 20 mg, respectively daily during a 2 month treatment period. Results: Placebo therapy did not significantly change insulin, adiponectin, glycated hemoglobin, and insulin sensitivity relative to baseline measurements. Rosuvastatin 5,10, and 20 mg dose-dependently and significantly improved flow-mediated dilation (34, 40, and 46%) after 2 months therapy when compared with baseline ( P &lt;0.001 by paired t -test) or when compared with placebo ( P &lt;0.001 by ANOVA). Rosuvastatin 5,10, and 20 mg dose-dependently and significantly increased insulin (median % changes; 16, 20, and 20%, respectively) and glycated hemoglobin levels (mean % changes; 2, 2, and 3%, respectively), and decreased adiponectin levels (mean % changes; 3, 9, and 14%, respectively) and insulin sensitivity (mean % changes; 2, 3, and 4%, respectively) after 2 months therapy when compared with either baseline (all P &lt;0.05 by paired t -test). These effects with rosuvastatin 5,10, and 20 mg were significant when compared with placebo ( P =0.006 for insulin, P =0.012 for glycated hemoglobin, P =0.007 for adiponectin, and P =0.002 for insulin sensitivity by ANOVA). Conclusions: Despite beneficial reductions in LDL cholesterol and improvement of flow-mediated dilation, rosuvastatin treatment dose-dependently and significantly resulted in decreasing insulin sensitivity and increasing ambient glycemia by reducing adiponectin levels and increasing insulin levels in hypercholesterolemic patients.
Abstract 18000: The Role of X-box Binding Protein 1 Splicing in Smooth Muscle Cell Proliferation and Neointima Formation
Authors: Lingfang Zeng, Yi Li, Yanhua Hu, Qingbo Xu
Journal: Circulation (2013)

Background: Smooth muscle cell (SMC) proliferation plays an important role in neointima formation in response to vascular injury. However, the underlying mechanism is still not well understood. It has been well documented that endoplasmic reticulum (ER) stress plays a provoking role in cardiovascular disease including neointima formation. As one of the key transducer in ER stress response, the X-box binding protein 1 (XBP1) has been demonstrated to contribute to endothelial cell proliferation, autophagic response and apoptosis, but less is known about its role in SMC growth. Methods and Results: In this study, we intend to study the role of XBP1 in SMC proliferation and its contribution to neointima formation in response to vascular injury. Quantitative RT-PCR and immunohistological staining analysis revealed that XBP1 splicing was up-regulated in the arterial vasculature in aged ApoE deficient mice and in response to vascular injury in wild type mice with elevated XBP1 protein in the neointima. Platelet derived growth factor (PDGF) induced XBP1 splicing via the interaction between PDGF receptor and inositol requiring enzyme 1 alpha (IRE1α). Transient over-expression of the spliced XBP1 (XBP1s) increased SMC proliferation, while knockdown of XBP1 or IRE1α abolished PDGF-induced SMC proliferation. XBP1s down-regulated calponin H1 gene expression at mRNA and protein levels, which might be through the down-regulation of TGFβ3 signalling. Reconstitution of calponin H1 via adenoviral transfer could ablate XBP1s-induced SMC proliferation. Addition of exogenous TGFβ3 abolished XBP1s-induced calponin H1 suppression and SMC proliferation. High levels of TGFβ3 and calponin H1 were detected in SMCs isolated from SM22-Cre/XBP1 loxP mice. These SMCs showed retardation in proliferation as compared to SMCs from wild type litters. Importantly, in the femoral artery injury model, XBP1 deficiency in SMCs prevented the neointima formation. CONCLUSION: XBP1 splicing plays an important role in SMC proliferation via regulating calponin H1 expression. Targeting XBP1 splicing in SMC may provide a novel therapeutic strategy to intervene neointima formation.
Abstract 18087: Docosahexaenoic Acid Complexed to Albumin as a Promising Neuroprotectant in Brain Ischemia
Authors: Ludmila Belayev, Larissa Khoutorova, Andre Obenaus, Tiffany N Eady, Nicolas G Bazan
Journal: Circulation (2013)

Background: Recently we have shown that docosahexaenoic acid (DHA), a component of fish oil, complexed to human serum albumin (Alb) is highly neuroprotective after experimental stroke in young rats. The purpose of this study was to determine whether treatment with DHA-Alb complex would be protective in aged rats after focal cerebral ischemia. Methods and Results: Isoflurane/nitrous oxide-anesthetized normothermic (brain temperature 36-36.5 o C) Sprague-Dawley aged rats (18-months old) received 2 h middle cerebral artery occlusion (MCAo) by poly-L-lysine-coated intraluminal suture. The neurological status was evaluated during occlusion (60 min) and on days 1, 2, 3 and 7 after MCAo; a grading scale of 0-12 was employed (normal score=0, maximal deficit=12). DHA (5mg/kg), Alb (0.63g/kg), DHA-Alb (5mg/kg+0.63g/kg) or saline was administered i.v. 3 h after onset of stroke (n=8-10 per group). Ex vivo T2-weighted imaging (T2WI) of the brains was conducted on an 11.7T MRI on day 7 and 3D reconstructions were generated. Infarct volumes and number of GFAP (reactive astrocytes), ED-1 (activated microglia/microphages), NeuN (neurons)-positive cells and SMI-71 (positive vessels) were counted in the cortex and striatum at the level of the central lesion. Physiological variables were entirely comparable between groups. Animals treated with DHA-Alb showed significantly improved neurological scores compared to vehicle rats; 33% improvement on day 1; 39% on day 2; 41% on day 3; and 45% on day 7. Total and cortical lesion volumes computed from T2WI were significantly reduced by DHA-Alb treatment (62 and 69%, respectively). In addition, treatment with DHA-Alb reduced cortical and total brain infarction while promoting cell survival. Conclusions: We conclude that DHA-Alb therapy is highly neuroprotective in aged rats following focal cerebral ischemia and has potential for the effective treatment of ischemic stroke in aged individuals.
Abstract 18089: Functional Mitral Regurgitation in Patients With Ischemic Cardiomyopathy Undergoing Surgical Ventricular Restoration for Anterior Aneurysm: Echocardiographic Findings and Clinical Impact
Authors: Andrea Garatti, Serenella Castelvecchio, Francesco Bandera, Marco Guazzi, Lorenzo Menicanti
Journal: Circulation (2013)

Objective: to evaluate clinical impact of severe functional mitral regurgitation(MR) in patients with dilatative post-ischemic CMP submitted to Surgical Ventricular Restoration(SVR). Methods: Among 445 consecutive patients operated of SVR for anterior aneurysm at our Institution between July 2001 and December 2011, 337(76%) patients presented with MR&lt;2+(Group A,mean age 65±10yrs) while moderate to severe MR(3-4+) was evident in 108(24%) patients(Group B,mean age 64±9yrs;). LV volumes(p=.019), LV sfericity index(p=.004) and mitral tenting area(p=.005) resulted independent predictor of severe MR at presentation(Figure 1). Results: All patients underwent standard SVR with exclusion of antero-septal akinetic area. CABG was concomitantly performed in 414 patients(93%; mean number of graft=2.7±1.5). All patients in Group B underwent mitral annuloplasty; on the opposite, mitral repair was performed in 18 patients(5%) of GroupA, who presented with annular enlargement &gt; 40mm. Thirty-days mortality was significantly higher in Group B(15%vs6%; p=.006). Seventy-five patients(22%) in Group A and 46 patients(43%) in Group B died at follow-up(p=.001). Kaplan-Meyer 5 and 10 years cumulative survival were significantly higher in group A(p=.008). Despite identical early mitral repair success rate, 15(7%) and 22(35%) patients in group A and B respectively(p=.001) showed long-term recurrence of severe MR. At Cox regression analysis preoperative mitral annulus dimension and postoperative systolic conicity index were the only independent predictors of late MR recurrence. Long-term 5 and 10 years survival(p=.037) as well as 5 and 10 years freedom from HF readmission(p=.001) were significantly affected by MR recurrence at FU. Conclusion: Severe preoperative MR significantly impacts surgical risk of SVR as early and long-term mortality. Furthermore, despite early succesfull surgical repair, severe MR recurrs in nearly a third of the discharged patients.
Abstract 18033: The Contribution of Cardiovascular Spending to Total Inpatient Spending for High-Cost Patients
Authors: Karen E Joynt, Atul Gawande, E. John Orav, Ashish Jha
Journal: Circulation (2013)

Spending in the Medicare program is concentrated among a small group of patients. As novel payment mechanisms such as bundled payments and accountable care organizations proliferate, there is increasing importance to understanding where these patients’ costs originate. Cardiovascular care is an area of focus, due to the high costs and expensive technologies used within the field. However, the contribution of cardiovascular spending to total inpatient spending for high-cost patients is unknown. We used standard 5% Medicare inpatient and outpatient files from 2009 and 2010 to evaluate the proportion of inpatient spending related to cardiovascular disease for high-cost patients (top 10% of spenders in 2010) and persistently high-cost patients (top 10% of spenders in 2009 and 2010). We classified all admissions using ICD-9 codes into clinical categories. We found that costs for cardiovascular care were highly concentrated, with 77% of cardiovascular inpatient spending from the 10% of patients in the high-cost cohort, and 25% of spending from the 3% of patients in the persistently high-cost cohort. Furthermore, cardiovascular care made up a significant proportion of total hospital spending for the high-cost cohort. Ischemic heart disease, congestive heart failure, arrhythmias, stroke and transient ischemic attack, peripheral atherosclerosis, cardiac valvular disease, and angina made up 22.6% of inpatient spending for high-cost patients and 19.7% of inpatient spending for persistently high-cost patients (Table). Projected to the national Medicare population, these admissions cost more than $10 billion in 2010. In conclusion, cardiovascular spending is highly concentrated, and cardiovascular disease comprises a large portion of inpatient spending for the most expensive Medicare patients. There is a tremendous opportunity for the cardiovascular community to target high-cost patients and pursue care redesign to lower costs for these common conditions.