tbuckley/cabot-search huggingface dataset:
Abstract 9990: Activation of Natural Killer T Cells Ameliorates the Development of Angiotensin II-mediated Abdominal Aortic Aneurysm Formation in Obese <i>ob/ob</i> Mice
Authors: Akimichi Saito, Naoki Ishimori, Satoshi Tokuhara, Atsushi Nozawa, Mikito Nishikawa, Hiroyuki Tsutsui
Journal: Circulation (2012)

Objective: Abdominal aortic aneurysm (AAA) is strongly associated with common atherosclerotic risk factors such as male gender, age, smoking, hypertension, and dyslipidemia. Its underlying cause has been considered to be atherosclerosis in which chronic inflammation including various pro-inflammatory cytokines within the vasculature is involved. We have demonstrated that natural killer T (NKT) cells, a unique subset of T lymphocytes which recognize glycolipid antigens and secrete a large amount of Th1/Th2 cytokines on activation, have a crucial role in the development of atherosclerosis and its plaque rupture as well as metabolic derangements in obese mice. However, it remains unclear that NKT cells are also involved in the development of AAA. Methods and Results: Male obese ob/ob mice were administered angiotensin II (AngII, 1000ng/kg/min; n=18) or phosphate buffered saline (PBS; n=10) with osmotic minipumps for 4 weeks. The AngII-administered mice were further divided into 2 groups; α-galactosylceramide (αGC, 0.1 μ g/g body weight intraperitoneal injection; AngII-αGC; n=12), which specifically activates NKT cells, and PBS (AngII-PBS; n=6). The maximal abdominal aortic diameter was significantly greater in AngII-PBS than in PBS (1726±288 vs. 833±69 µm, p &lt;0.01). AngII administration significantly enhanced mRNA expression of the activation markers of macrophages, F4/80 and major histocompatibility complex (MHC)-class II, by 2.5-folds and 4.6-folds ( p &lt;0.05 each), and matrix metalloproteinase-2 (MMP-2) by 5.0-folds ( p &lt;0.01) in aortic tissues from AngII-PBS mice. αGC injection significantly ameliorated the AngII-mediated increase of aortic diameter in AngII-αGC (1241±257 µm, p &lt;0.01 vs. AngII-PBS) without affecting the blood pressure (145±6 vs. 154±5 mmHg, p =N.S.). Conclusions: AngII induces AAA in obese ob/ob mice via activating macrophage infiltration and up-regulation of MMP-2 within the vascular tissues. The activation of NKT cells can ameliorate the development of AAA. Regulation of NKT cell activation may be a novel therapeutic strategy against AAA.
Abstract 9936: Cardiac Magnetic Resonance Factors Associated With Successful Univentricular to Biventricular Conversion in Small Left Hearts
Authors: Puja Banka, Barbara Schaetzle, Sitaram Emani, Pedro Del Nido, Tal Geva, Andrew J Powell
Journal: Circulation (2012)

Background: In patients (pts) with small left heart structures, the decision to attempt conversion from a univentricular to biventricular (BiV) circulation has profound consequences, but preoperative factors predicting success are not well established. We sought to identify cardiac magnetic resonance imaging (CMR) parameters associated with successful BiV conversion. Methods: All pts with hypoplastic left heart structures and univentricular physiology who underwent CMR prior to an attempted BiV conversion were retrospectively identified. Subjects were divided into 2 anatomic groups: 1) right-dominant atrioventricular canal defect (AVC), and 2) small left heart structures without an AVC defect (SLH). Successful BiV conversion was defined as a BiV circulation at latest follow-up. Results: In the SLH group, there were 20 pts who underwent BiV conversion at a median age of 38.5 months (0-82) and 15 (75%) were successful with a median follow-up of 12 months (0-64). Pts with successful BiV conversion had a higher median left ventricular end-diastolic volume (LVEDV) (61 vs. 27 ml/m 2 , p=0.006), higher median LV/RV stroke volume ratio (0.9 vs. 0.2, p=0.004), and a trend towards higher median mitral/tricuspid inflow ratio (1.1 vs. 0.7, p=0.08). LVEDV ≥30 ml/m 2 was associated with higher percentage of successful conversion (88 vs. 25%, p=0.02); 3 of the 4 pts with LVEDV &lt;30 ml/m 2 were unsuccessful. Late gadolinium enhancement (LGE) consistent with endocardial fibroelastosis (EFE) was present in 15 pts (75%) and was not associated with failed conversion (p=0.56), although 14 pts (93%) underwent EFE resection either before or after CMR. In the AVC group, there were 10 pts who underwent BiV conversion at a median age of 6.5 months (2-75) and all were successful. Minimum values were LVEDV 22ml/m 2 , LV/RV stroke volume ratio 0.2, and mitral/tricuspid area ratio 0.3. None had LGE. Conclusion: In SLH pts, CMR derived LVEDV and LV/RV stroke volume ratio but not LGE are associated with successful BiV conversion. In AVC pts, the high rate of successful BiV conversion precluded discriminant analysis, but the range of CMR parameters permitting success is provided. These data aid in the interpretation of CMR results in pts being considered for a BiV conversion.
Abstract 9961: Semaphorin-induced Inflammation Contributes to Insulin Resistance in Dietary Obesity
Authors: Ippei Shimizu, Yohko Yoshida, Junji Moriya, Taro Katsuno, Masayoshi Suda, Yoshio Kobayashi, Tohru Minamino
Journal: Circulation (2012)

Ippei Shimizu, 2012 Finalist and Presenting Author
Abstract 11298: Aged Human Cells Rejuvenated by Cytokine-Enhancement of Biomaterials for Surgical Ventricular Restoration
Authors: Lu Sun, Kai Kang, Yun Xiao, Shu-Hong Li, Jun Wu, Terrence M Yau, Richard D Weisel, Milica Radisic, Ren-Ke Li
Journal: Circulation (2012)

Lu Sun, 2012 Finalist and Presenting Author
Abstract 9960: Electrocardiographic Intervals and Adverse Outcomes in People with Chronic Kidney Disease: Results from the Chronic Renal Insufficiency Cohort Study
Authors: Joshua M Arkin, Rajat Deo, Peter Yang, Xiaoming Zhang, Elsayed Z Soliman, Raymond Townsend, Michael G Shlipak, Harold I Feldman
Journal: Circulation (2012)

Background: Abnormalities in electrocardiographic (ECG) intervals have been associated with death and heart failure. We sought to evaluate whether abnormal ECG intervals are associated with adverse events among people with chronic kidney disease (CKD). Methods: We evaluated standard baseline ECGs among 3669 participants from the Chronic Renal Insufficiency Cohort Study (CRIC). The association between each of the ECG intervals (PR, QRS, QT and RR) and death, heart failure and the composite, myocardial infarction (MI), peripheral arterial disease (PAD) or stroke was assessed using Cox proportional hazards models. Multivariate analysis included adjustment for demographics, comorbidities, medications and electrolytes. A sensitivity analysis included an assessment of ECGs among the subgroup without baseline cardiovascular disease (CVD). Results: After a mean follow-up duration of 5 years, abnormal ECG intervals were associated with an increased incidence of adverse outcomes (Figure 1). The adjusted risk of death was increased among participants with a QRS&gt;100 milliseconds (msec) (HR 1.53 [95%CI 1.21-1.95]), QTc &gt;440 msec (HR 2.15 [95%CI 1.69- 2.74]) and RR&lt;600msec (HR 4.20 [95%CI 1.68-10.51]) compared to participants with a normal QRS, QTc and RR duration, respectively. Abnormal ECG intervals were also independent risk factors for death and the cardiovascular endpoints after excluding participants with prevalent CVD at baseline. Conclusion: Cardiac conduction disease in CKD participants, including the subgroup without a history of CVD, is strongly associated with an increased risk of adverse outcomes including death. Future studies need to evaluate whether ECG variables can be effective measures for risk stratification in this high risk subgroup of the population.
Abstract 9908: Function and Regulation of the Adipocytokine Ctrp9 in a Mouse Model of Ischemia/reperfusion Injury
Authors: Kambara Takahiro, Koji Ohashi, Rei Shibata, Yoshiyuki Kataoka, Yasuhiro Ogura, Sonomi Maruyama, Takashi Enomoto, Yusuke Uemura, Toyoaki Murohara, Noriyuki Ouchi
Journal: Circulation (2012)

Background: Acute coronary syndrome is a leading cause of mortality worldwide. Obesity-related disorders are associated with an increased prevalence of cardiovascular disease as well as an increased cardiac damage after acute coronary syndrome. Although C1q/TNF-related protein (CTRP) 9 is an adipocytokine with beneficial properties for glucose metabolism and endothelial function, nothing is known about the role of CTRP9 in ischemic heart disease. Here we investigated the effect of CTRP9 on acute myocardial injury in a mouse model and examined the regulation of adipocyte CTRP9. Methods and Results: Wild-type (WT) mice were subjected to 60 minutes of myocardial ischemia followed by 24 hours of reperfusion. An adenoviral vector expressing CTRP9 (Ad-CTRP9) or β-galactosidase as a control was intravenously injected into WT mice 3 days before surgery. Administration of Ad-CTRP9 reduced infarct size and myocyte apoptosis following myocardial ischemia/reperfusion, which was associated with an elevated phosphorylation of AMP-activated protein kinase (AMPK) in ischemic heart. In cultured cardiac myocytes, treatment with CTRP9 protein attenuated apoptosis during hypoxia/reoxygenation and enhanced AMPK signaling. Meanwhile, inhibition of AMPK activity blocked the anti-apoptotic effect of CTRP9. Plasma CTRP9 levels were reduced in diet-induced obese and genetic obese db/db mice. In addition, myocardial ischemia/reperfusion resulted in a significant reduction of circulating CTRP9 levels with decrease in its expression in adipose tissue. After reperfusion, the expression of inflammatory cytokines and NADPH oxidase components was upregulated in adipose tissue, which was accompanied by increased plasma free fatty acid levels. Treatment of adipocytes with palmitic acid or the inducers of inflammation and oxidative stress reduced CTRP9 expression. Furthermore, systemic delivery of CTRP9 protein at the time of reperfusion attenuated myocardial infarct size in response to ischemia/reperfusion. Conclusion: CTRP9 exerts a cardioprotective action during ischemia/reperfusion via AMPK-dependent mechanism. Thus, the enhancement or supplementation of CTRP9 can be novel therapeutic strategies for the treatment of acute coronary syndrome. .
Abstract 9902: Tricuspid Valve Annuloplasty with Edge-to-Edge Repair is Effective Strategy for Management of Functional Tricuspid Regurgitation
Authors: Manatomo Toyono, Jose L Navia, Takahiro Shiota
Journal: Circulation (2012)

Introduction: Tricuspid valve (TV) annuloplasty is recommended for management of functional tricuspid regurgitation (TR); however, residual TR occurs up to 25% of patients after surgery. For management of mitral regurgitation, edge-to-edge repair is accepted as effective procedure. Hypothesis: TV annuloplasty with edge-to-edge repair is more effective for management of functional TR than isolated TV annuloplasty. Methods: We analyzed 216 patients who underwent isolated TV annuloplasty and 75 patients who underwent TV annuloplasty with edge-to-edge repair. Echocardiography was performed to assess response to surgery and cardiac function and geometry 21 ± 5 days before and 6 ± 4 days after surgery. Severity of TR was assessed by maximal jet area in the right atrium. Residual TR was defined as maximal TR jet area &gt;5 cm 2 after surgery. Results: There was no significant difference in preoperative functional TR jet area between patients who underwent isolated TV annuloplasty and those who underwent TV annuloplasty with edge-to-edge repair (Table). Patients who underwent isolated TV annuloplasty showed significantly greater TV annulus diameter and lower right ventricular fractional area shortening than those who underwent TV annuloplasty with edge-to-edge repair. In both groups, TR jet area was significantly decreased after surgery. Patients who underwent TV annuloplasty with edge-to-edge repair showed significantly lower postoperative TR jet area as compared with those who underwent isolated TV annuloplasty although mean postoperative TR jet areas were &lt;5 cm 2 in both groups. Patients who underwent TV annuloplasty with edge-to-edge repair showed significantly less residual TR as compared with those who underwent isolated TV annuloplasty. Conclusions: TV annuloplasty with edge-to-edge repair is effective procedure for management of functional TR and may be superior to isolated TV annuloplasty.
Abstract 9937: The Impact of Wall Thickness and Saccular Geometry on the Computational Wall Stress of Descending Thoracic Aortic Aneurysms
Authors: Eric K Shang, Derek P Nathan, Sarah C Vigmostad, Ronald M Fairman, Robert C Gorman, Joseph H Gorman, Krishnan B Chandran, Benjamin M Jackson
Journal: Circulation (2012)

OBJECTIVES: Wall stress calculated using finite element analysis (FEA) has been used to predict rupture risk of aortic aneurysms. Prior models often assume uniform aortic wall thickness and fusiform geometry. We examined the effects on peak wall stress (PWS) of including local wall thickness, intraluminal thrombus (ILT), and calcifications in FEA of descending thoracic aortic aneurysms. We further investigated the differences in PWS between saccular and fusiform aneurysms. METHODS: CTAs in patients with descending thoracic aortic aneurysms (n=10 total, 5 fusiform and 5 saccular) were analyzed with custom algorithms. For each patient, a control model was defined with uniform wall thickness. Experimental models added the effects of: variable wall thickness (VWT), ILT, and calcifications. A final, combined model incorporated all features. Commercial FEA software was used to load each model with 120 mmHg pressure and compute Von Mises PWS. RESULTS: The mean (n=10) PWS of the control models was 410±111 kPa. The imposition of VWT increased PWS (481±126 kPa, P&lt;0.001) (see Figure). The addition of ILT to VWT (359±86 kPa, p=&lt;0.001) reduced PWS, while the addition of calcifications was not statistically significant (506±126 kPa, P=0.07). The final combined model also reduced PWS (368±88 kPa, P&lt;0.001). Saccular aneurysms had significantly increased stress compared to fusiform aneurysms when normalized by aortic diameter in the control model (104±14 kPa/cm, P=0.04 vs 87±8), but not in the combined model (77±7 kPa/cm vs 67±12, P=0.22). CONCLUSIONS: Incorporation of local wall thickness can significantly increase PWS in FEA models of thoracic aortic aneurysms. Incorporating variable wall thickness, ILT, and calcifications significantly impacts computed PWS of thoracic aneurysms; sophisticated models may therefore be more accurate in assessing rupture risk. Saccular aneurysms did not demonstrate a significantly higher normalized wall stress than fusiform aneurysms.
Abstract 13282: Aspirin Exposure Reveals Novel Genes Associated with Platelet Function and Cardiovascular Events
Authors: Deepak Voora, Derek Cyr, Joseph Lucas, Tsan Chi, Timothy McCaffrey, Richard Katz, L. Kristin Newby, William Kraus, Richard Becker, Thomas Ortel, Geoffrey Ginsburg
Journal: Circulation (2012)

Deepak Voora, 2012 Finalist and Presenting Author
Abstract 18898: Characterization of Proendothelin-1 Derived Peptides Identifies a Co-secreted Modulator of ET-1 Vasoconstriction, and Provides Insights for Biomarker Measurements
Authors: Jale Yuzugulen, Elizabeth G Wood, Julie A Douthwaite, Inmaculada C Villar, Nimesh S Patel, James Jegard, Alexander Montoya, Pedro Cutillas, Oliver Hartley, Amrita Ahluwalia, Roger Corder
Journal: Circulation (2012)

Background: ET-1 is strongly implicated in cardiac and renal pathologies both as a potent vasoconstrictor, and as an inducer of tissue remodeling and fibrosis. However, in experimental and human studies ET antagonists are often ineffective. ET-1 biosynthesis occurs via a 212 amino acid peptide preproendothelin-1 (ppET-1); hence other peptides from this precursor may contribute to the biological effects of EDN1 gene expression. Methods: Specific immunoassays were used to identify the peptide products of ppET-1 in conditioned media samples from EA.hy 926 and A549 cell lines. Secretion of proET-1 peptides was also investigated using primary cultures of human aortic endothelial (HAEC) and smooth muscle cells (HAVSMC), and cardiomyocytes (HCM). Synthetic proET-1 peptides were used to study their rate of clearance from the circulation in anaesthetized rats, and effects on ET-1 induced vasoconstrictor and blood pressure responses. Results: Using specific antibodies 3 peptides were identified: NT-proET-1 (ppET-1[18-50]), MP-proET-1 (ppET-1[93-166]) and CT-proET-1 (ppET-1[169-212]). Specific sandwich ELISAs for these three peptides showed that they were secreted from all cell types studied with levels of release correlating with ET-1. Arterial blood measurements after i.v. administration (1 nmol/kg) of peptide showed markedly different elimination rates. NT-proET-1 had the most rapid clearance (&lt;5 min) and CT-proET-1 the slowest (8% of initial values 40 min after injection). On rat mesenteric resistance arteries MP-proET-1 alone showed no significant vasoconstrictor effect up to 10 nM, but after pre-treatment with ET-1 (1 - 3 nM) it produced a concentration dependent vasoconstriction. Pre-incubation of rat mesenteric resistance arteries with 10 nM MP-proET-1 increased the response of 1 nM ET-1 by 5 fold (P &lt;0.002). MP-proET-1 alone (3 nmol/kg) had no effect on blood pressure in anaesthetised rats, but it significantly increased the duration of the pressor response to ET-1 (0.3 nmol/kg, P &lt;0.02). Conclusions: ProET-1 derived peptides may play an important role in vascular pathologies by modulating ET-1 responses, or the actions of other mediators. The slower systemic clearance of CT-proET-1 favors its use as a biomarker of EDN1-linked pathologies.
Abstract 14933: Effect of Atherogenic Diets with Different Ratios of Omega-6 Polyunsaturated Fatty Acids to Eicosapentaenoic Acid Plus Docosahexaenoic Acid on Lipid Content and Inflammatory Response in Hepatic and Visceral Adipose Tissue in LDL Receptor Null Mice
Authors: Shu Wang, Bradley Miller, Nirupa R Matthan, Dayong Wu, Alice H Lichtenstein
Journal: Circulation (2012)

Shu Wang, 2012 Finalist and Presenting Author
Abstract 12746: Hydrogen Inhalation Improves Neurological and Cardiac Outcome in a Rat Model of Cardiac Arrest With Ventricular Fibrillation
Authors: Kei Hayashida, Motoaki Sano, Naomi Kamimura, Takashi Yokota, Masaru Suzuki, Yuichiro Maekawa, Akio Kawamura, Shigeo Ohta, Keiichi Fukuda, Shingo Hori
Journal: Circulation (2012)

Kei Hayashida, 2012 Finalist and Presenting Author
Abstract 15061: Mst1-Mediated Phophorylation of Foxo1 and C/EBP-β Stimulates Cell Protective Mechanisms In Cardiomyocytes
Authors: Yasuhiro Maejima, Zhai Peiyong, Liu Tong, Li Hong, Sadoshima Junichi
Journal: Circulation (2012)

Yasuhiro Maejima, 2012 Finalist and Presenting Author
Dancing in the Heart of Organellar Proteomes
Authors: Peipei Ping
Journal: Circulation (2012)

The rapid development of high accuracy and high sensitivity mass spectrometry technologies has revolutionized our understanding of proteins and their contribution to cellular function. However, there is an increasingly apparent disconnect between these state-of-the-art tools and their effective applications to advance cardiovascular biology and medicine. Despite progress made in certain areas of investigation, cardiovascular proteomic research faces three major challenges: lack of study designs to accurately pinpoint connections between function and proteomes; limited quantitative information to understand the dynamics of proteomes in disease phenotypes; and the overwhelming quantity and fragmented nature of mass spectra datasets lacking functional annotations. This 2012 Thomas Smith Lecture presentation will provide an overview of the accomplishments in cardiovascular proteomics, highlight the barriers and opportunities in this field, and address the aforementioned obstacles using examples from organellar proteomics investigations, whereby model systems and computational tools are combined to understand human diseases.
Cryptogenic Stroke: Search Your Heart!
Authors: Scott E. Kasner
Journal: Circulation (2012)

About 30-40% of all ischemic strokes are classified as cryptogenic because no well defined cause can be identified. Without a known cause, the treatment is arbitrary, usually defaulting to antiplatelet therapy and the risk of future stroke is uncertain. Cryptogenic stroke is an imprecise term that includes four subcategories: strokes without a sufficient evaluation, those with a thorough but seemingly negative evaluation, those that don't strictly meet criteria for other established causes, and those with multiple competing causes. High risk etiologies that are often missed include aortic arch atherosclerosis, paroxysmal atrial fibrillation, and akinetic left ventricular segments. The risk related to a low ejection fraction or an enlarged left atrium has been incompletely studied. The role of patent foramen ovale in the pathogenesis of cryptogenic stroke remains complex and unresolved. Rare causes often are not considered at all. Specific attention to detecting these cardiac problems with echocardiography and prolonged rhythm monitoring could cut the proportion of cryptogenic strokes by as much as half and result in improved prevention of recurrent stroke.
Abstract 16619: Bendopnea, a Novel Symptom of Heart Failure, is Mediated via Elevated Left Ventricular Filling Pressures
Authors: Jennifer T. Thibodeau, T. Turer Aslan, K Gualano Sarah, R Ayers Colby, D. Mishkin Joseph, C. Patel Parag, P.A. Mammen Pradeep, W. Markham David, D. Levine Benjamin, H. Drazner Mark
Journal: Circulation (2012)

Jennifer T. Thibodeau, 2012 Finalist and Presenting Author
Abstract 9932: Chronic Urotensin II Receptor Blockade Causes Regression of Heart Failure: Beneficial Effects on Neurohormonal Activation, Cardiomyocyte Contractile Function [Ca <sup>2+</sup> ]i Regulation and Beta-Adrenergic Modulation
Authors: Che Ping Cheng, Peng Zhou, Heng-Jie Cheng, Qun Shao, David C Sane, William C Little
Journal: Circulation (2012)

Background. Heart failure (HF) is associated with increased levels of urotensin-II (UII) and upregulation of UII-mediated cardiac inhibitory pathway. This suggests that cardiac UII activation contributes to HF progression and may be a therapeutic target. However, the role and mechanism of chronic UII receptor antagonist (UII-ANT) in HF are unclear. We assessed the hypothesis that blocking UII improves cardiomyocyte function, [Ca 2+ ] i regulation, and β-adrenergic receptor (AR) signaling effectiveness, thus limiting HF progression. Methods. We compared sympathetic nervous system (SNS) activation, LV myocyte β 1 -AR protein expression, and myocyte contractile and Ca 2+ current (I Ca,L ) responses to isoproterenol (ISO) in 3 groups of age-matched adult mice (8/group) over 8 weeks (W): 1) HF [after onset of HF induced by ISO (170 mg/kg sq for 2 days) for 4 W and then receiving placebo], 2) HF/UII-ANT [after onset of HF and then receiving urantide, a potent UII-ANT (10 -5 M/kg/day sq via osmotic mini pump), given for 4W], and 3) C (controls). Results. Compared with C, ISO-treated mice had established HF with significantly increased plasma norepinephrine (NE) (3474 vs 668 pg/ml) and decreased ejection fraction (EF, 35% vs 63%). In HF, cardiomyocyte basal functional performance and I Ca,L were significantly depressed with 42% reductions in cell contraction (dL/dt max , 78 vs 134 µm/s), relaxation (dR/dt max , 69 vs 120 µm/s) and a 48% decreased I Ca,L (3.7 vs 7.2 pA/pF). Importantly, compared with normal myocytes, superfusion of ISO (10 -8 M) caused significantly less increases in dL/dt max (30% vs 69%), dR/dt max (29% vs 64%), and I Ca,L (12% vs 36%) in HF myocytes. These changes were associated with significantly decreased myocyte β 1 -AR (0.37 vs 0.61) protein. In HF/UII-ANT mice, plasma NE (908 pg/ml), EF (59%), and myocyte β 1 -AR (0.57) expression returned close to C levels. Basal myocyte contraction and I Ca,L significantly improved, and ISO-induced increase in dL/dt max (66%), dR/dt max (60%), and peak I Ca,L (34%) were significantly augmented. Conclusion. Chronic UII-ANT prevents HF-induced SNS activation and downregulation of LV myocyte β 1 -ARs and leads to the preservation of myocyte function, I Ca,L , and β-adrenergic responsiveness in a mouse model of progressive HF.