tbuckley/cabot-search huggingface dataset:
Abstract 19007: Lineage Reprogramming of Mouse Fibroblasts to Induced Cardiac Progenitor Cells by Defined Factors
Authors: Pratik A Lalit, Martin Lea, Steven A Jackson, Brian E McIntosh, Michael Kyba, James A Thomson, Daniel J Garry, Timothy J Kamp
Journal: Circulation (2013)

Several studies have reported reprogramming of mouse fibroblasts to induced cardiomyocytes (iCMs). However, reprogramming to cardiac progenitor cells (CPCs), which may be more favorable for cell therapy because of their proliferative properties and multipotency, remains to be accomplished. This study aims to reprogram mouse fibroblasts to induced CPCs (iCPCs) by transcription factor (TF)-mediated reprogramming. We have cloned a library of 25 genes including cardiac-related TFs and chromatin remodeling agents into a novel, inducible piggyBac transposon vector. Fibroblasts were derived from a Nkx 2.5- YFP cardiac progenitor reporter mouse model. We first confirmed efficient transcription/translation of our piggyBac TF library. Next, as a control experiment neonatal cardiac fibroblasts were transfected with Gata4, Mef2c, Tbx5 or Gata4, Mef2c, Tbx5, Hand2 (published factors) and monitored for appearance of beating cells. Spontaneously beating, YFP- iCMs were observed only after application of doxycycline (25 days) for both combinations of factors, demonstrating a robust reprogramming system. We then transfected neonatal cardiac fibroblasts with entire library of 25 factors and observed YFP+ cells on doxycycline treatment. The TF pool was subsequently narrowed down to 11 essential factors. On transfection with 11 factors, YFP+ cells were first observed 4 days after doxycycline treatment. By day 20 these YFP+ cells developed into two-dimensional, highly proliferative YFP+ colonies of cells that lost their parental fibroblast morphology and exhibited a high nucleus to cytoplasmic ratio. Similar reprogramming was later accomplished using adult cardiac and adult lung fibroblasts. Untransfected/iPSC factors transfected control fibroblasts yielded no beating or YFP+ cells. qPCR analysis of these YFP+ colonies revealed an upregulation of CPC markers including Mesp1, Mef2c, Irx4 accompanied with down regulation of fibroblast specific genes such as Fsp1, consistent with reprogramming towards an iCPC state. These results support the ability of inducible piggBac-based TFs to reprogram fibroblasts to iCPCs. Current experiments are focused on optimizing culture conditions to maintain iCPCs in a proliferative state and defining their potency.
Abstract 13444: Mechanism of Extravasation of Infused Regenerative Cells from Microvessels into Tissue Parenchyma
Authors: Ke Cheng, Deliang Shen, Baiming Sun, Yucai Xie, Eugenio Cingolani, Konstantinos Malliaras, Doan Tran Duong, Supurna Chowdhury, Eduardo Marban
Journal: Circulation (2012)

Ke Cheng, 2012 Finalist and Presenting Author
Haldane, Hot Dogs and Halitosis: The Anion Nitrite As an Intrinsic Hypoxic Signaling Molecule and New Therapy for Pulmonary Arterial Hypertension
Authors: Mark Gladwin
Journal: Circulation (2012)

Nitrate and nitrite have traditionally been considered dietary toxins that increase the risk of stomach cancer. In this lecture we discuss how the scientific discovery was made that nitrate and nitrite are in fact natural signaling pathways in the human body. Nitrite is now considered a biological reservoir of nitric oxide (NO), present in plasma, red cells and organ systems, that is reduced to NO during physiological and pathological hypoxia. Current studies by multiple research groups indicate that dietary and NOS-dependent nitrite formation may contribute to critical physiological functions such as blood pressure control, hypoxic vasodilation, mitochondrial respiration and the cellular resilience to ischemic stress. Recent studies suggest that a number of cellular enzymes regulate nitrite reduction to NO at different oxygen tensions, with organ system specificity. The role of molybdenum containing enzymes and heme-globin superfamily proteins - hemoglobin, myoglobin, neuroglobin, cytoglobin and the plant and drosophila hemoglobins - are the subject of active current study, and recent advances in this area of investigation will be reviewed. Studies of cytochrome C oxidase, neuroglobin and plant hemoglobins have identified a role for heme coordination in the control of nitrite reduction to NO (six-to-five coordinate regulation of nitrite binding and reduction). New pre-clinical and clinical studies suggest that inhaled and oral nitrite may be able to prevent and reverse established pulmonary arterial hypertension and phase II proof of concept trials are currently in progress in the US and Europe. It is proposed that the nitrate - nitrite - NO pathway represents a fundamentally conserved pathway for energetics and signaling in biology.
JD Souther
Journal: Circulation (2012)

Dr. William J. Rashkind and his family established this lecture in 1986 shortly before his death. Dr. Rashkind was an internationally known pediatric cardiologist credited for developing balloon atrial septostomy, also known as the Rashkind procedure. Dr. Rashkind was an active volunteer for the American Heart Association at the national and state levels. This lecture is made possible by a grant from the late Dr. Rashkind and his family. In honor of the 26th anniversary of the Rashkind Lecture, the Council on Cardiovascular Disease in the Young is pleased to welcome JD Souther. Mr. Souther, a multi-Grammy Award winner, who has written and recorded hit songs with artists such as James Taylor, Linda Ronstadt and the Eagles. He's a terrific performer - a co-star on the new ABC series, “Nashville” - and hit songs all play off the beat of the heart. There will be a little singing, a little talk and some Q &amp; A with multi-platinum singer-songwriter - and co-star of the new ABC drama series “Nashville.”
Abstract 14763: Hypoxia-Mediated Activation of Notch Signaling Enhances Store-Operated Calcium Entry in Pulmonary Arterial Smooth Muscle Cells
Authors: Kimberly A. Smith, Qiang Gou, Aya Yamamura, Hisao Yamamura, Jason X.-J Yuan
Journal: Circulation (2012)

Kimberly A. Smith, 2012 Finalist and Presenting Author
Abstract 15126: Weight and Risk Factor Modification: Impact on Atrial Fibrillation
Authors: Hany S Abed, A Wittert Gary, E Middledorp Melissa, G Shirazi Masoumeh, Bahrami Bobak, P Leong Darryl, F Lorimer Michelle, H Lau Dennis, G Brooks Anthony, P Abhayaratna Walter, M Kalman Jonathan, Sanders Prashanthan
Journal: Circulation (2012)

Hany S Abed, 2012 Finalist and Presenting Author
Abstract 11326: In vivo Study by Dynamic Contrast-enhanced Magnetic Resonance Imaging Suggests Biological Link between Adventitial Perfusion and Outward Remodeling
Authors: Jie Sun, Huijun Chen, William S Kerwin, Daniel S Hippe, Thomas S Hatsukami, Chun Yuan
Journal: Circulation (2012)

Jie Sun, 2012 Finalist and Presenting Author
Crippling Cardiovascular Disease With Kruppels
Authors: Mukesh Jain
Journal: Circulation (2012)

The metabolic and immune systems are evolutionary conserved, highly interdependent, and requisite for survival. Dysfunction of either system alters homeostasis and contributes to cardiovascular disease, cancer, and metabolic disorders. Studies from our laboratory have identified an essential role for a family of transcription factors termed Kruppel-like factors (KLFs) in innate immunity, metabolism, and the cardiovascular response to physiologic and pathologic stimuli. Mechanistically, this work has led to an appreciation of how KLFs intersect with nodal transcriptional and epigenetic pathways to exact their biological action. Here, I will first review how control of cellular inflammation and metabolism by KLFs impacts key steps in the pathogenesis of vascular disease, including endothelial dysfunction, immune cell activation, smooth muscle proliferation, and thrombosis. Next, I will discuss how KLFs coordinate systemic metabolic homeostasis by controlling flux of all three major cellular nutrient classes — glucose, amino acids, and lipids — observations that provide insights as to how diverse physiologic stimuli such as fasting, circadian rhythms, and exercise impact health. Finally, I will highlight the evidence linking KLFs to human disease and how these observations along with mechanistic insights are being exploited for therapeutic gain.
Abstract 9974: A Novel Comprehensive RV Strain Analysis: Echocardiographic Approach to Define a Normal Adult Population
Authors: Daniel E Forsha, Niels Risum, Phillip B Smith, Andrea Kropf, Sudarshan Rajagopal, Zainab Samad, Ronald J Kanter, Barker Piers, Joseph Kisslo
Journal: Circulation (2012)

Introduction: This study was performed to test the feasibility of and to establish normal ranges of a novel 3 view RV strain analysis. Such an approach is a necessary precursor for more detailed studies of RV regional dysfunction since RV failure is the primary problem in many congenital heart disorders. To date, 2D speckle-tracking strain experience with the RV is limited. Hypothesis: This novel methodology is feasible and will allow significantly improved RV data to be produced via strain analysis. Methods: Twenty-five healthy subjects were prospectively studied from the apical position using a 3 view RV approach with views equivalent to a LV 60º rotational model (Figure). Subjects received a complete echo optimized for 18 segment (SEG) RV strain analysis using a GE Vivid e9 with off-line 2D speckle-tracking analysis performed using EchoPAC BT11 software. Results: Mean age was 30 years (range 20-52, 36% male). All had a normal QRS duration, TAPSE, and LVEF. Adequate tracking was obtained in 457/468 of all segments (98%). Using global functional RV analysis, the global peak longitudinal systolic strain (PLSS) mean was -23.5% (range -18.1% to -27.3%). Regional PLSS was greatest in the free-wall &gt; apical &gt; septal segments (p&lt;0.001). The standard deviation of time to peak intervals (SDTTP) in the 18-SEG model was 26.7±8.2 ms (range 14.9 - 41.9ms) versus 22.5±9.2 ms in the traditional apical 4 chamber single view (p=0.004). No dyssynchronous patterns were observed. Coefficients of variation for independent intra/inter-observer measures were 6% and 9% for global PLSS and 12% and 11% for SDTTP. Conclusions: The 18-SEG regional RV strain analysis is feasible, and normal ranges follow a consistent synchronous pattern. This novel comprehensive methodology adds information to the traditional model and provides a baseline for further study of regional RV strain in patients with suspected RV dysfunction and/or abnormal contraction patterns.
Abstract 9912: Impact of Blood Pressure Lowering Therapy on Left Atrial Function and the Incidence of Atrial Fibrillation in Elderly Hypertensive Patients: Results from a Prospective Study with Speckle Tracking Echocardiography
Authors: Takatomo Watanabe, Masanori Kawasaki, Ryuhei Tanaka, Koji Ono, Maki Saeki, Hiroto Yagasaki, Shingo Minatoguchi, Hirotaka Miwa, Fumitaka Tokoro, Rieko Matsuoka, Shintaro Abe, Yoshiaki Goto, Takashi Kato, Shunichiro Warita, Tai Kojima, Makoto Iwama, Takeshi Hirose, Masashi Kawade, Toshiyuki Noda, Sachiro Watanabe, Shinya Minatoguchi
Journal: Circulation (2012)

Background: The risk of atrial fibrillation (AF) associated with left atrial (LA) remodeling is increasing in elderly patients with hypertension (HTN). We assessed the hypothesis that strict blood pressure (BP) lowering therapy has a beneficial effect on LA structure and function and may decrease the incidence of new-onset AF in elderly patients with HTN. Methods: First, we recruited 380 patients ≥65 years old with HTN. Exclusion criteria were secondary HTN, atrial arrhythmias, systolic dysfunction (left ventricular ejection fraction &lt;50%), congestive heart failure or myocardial infarction or stroke within the past six months, moderate to sever valvular disease. We divided 234 subjects ≥65 years old, (75±5 years old) into four groups based on mean office BP achieved over the past two years and followed up for two years: a normotensive group (n=71), a HTN group with good BP control (systolic BP &lt;130 and diastolic BP &lt;80 mmHg, n=72), a HTN group with poor BP control (systolic BP ≥140 or diastolic BP ≥90 mmHg, n=41) and a HTN group with moderate BP control (systolic BP ≥ 130 but &lt;140 and diastolic BP &lt;90 or systolic BP &lt;140 mmHg and diastolic BP &lt;90 but ≥80 mmHg, n=50). LA volume, emptying function (EF), strain and strain rate (SR) were measured by speckle tracking echocardiography at baseline and after two years. Results: LA volume, EF, strain and SR in the HTN group with good BP control were better preserved than those parameters in the HTN group with poor BP control at baseline and after two years. The incidence of new-onset AF during two years was significantly higher in the HTN group with poor BP control (hazard ratio: 7.015 (95% CI: 2.433 - 20.22), p&lt;0.001). Conclusion: LA structure and function were preserved in the HTN group with good BP control, and this was associated with preserved diastolic function and comparable to normal. Strict BP lowering therapy had a beneficial effect on LA structure and function and should be recommended to prevent new-onset AF even in elderly HTN patients.
Adventures (and Misadventures) on the Road to Understand (and Reduce) Disparities in Stroke Mortality
Authors: George Howard
Journal: Circulation (2012)

Racial and geographic disparities in stroke mortality have existed for over a half-century, and between ages of 45 to 65 are among the largest for any disease. For much of this period, the causes of the disparities have been mysterious; however, investments by NINDS and NHLBI are now providing insights regarding the causes of these disparities. Diverse and complementary study designs provide information on different aspects of the disparities in stroke. Vital statistics data track temporal patterns in stroke mortality, perhaps the ultimate index of the success in overcoming the disparities. Surveillance studies allow assessment of the contributions of incidence versus case fatality to the disparities in vital statistics mortality data, a distinction critical to effort to reduce the disparities. Finally, cohort studies give insights to the contribution of specific risk factors to disparities in either incidence or case fatality, allowing targeted interventions to be effective. While deaths from stroke mortality declined by a third over the most recent nine year period, there has been a 35% increase in the black-white disparity and little change in geographic disparities. Surveillance studies suggest that the black-white disparity is primarily attributable to differences in incidence, and also have unmasked Hispanic-white differences in incidence that are not apparent in mortality trends. Longitudinal cohort studies are suggesting multiple targets for intervention such as a multi-dimensional impact of blood pressure on the black-white differences, and indications that diet may be contributing to geographic disparities. The vital statistics mortality data currently provide a mixed message, with falling stroke mortality for all groups, but a more rapid fall for whites contributing to an increase in the magnitude of racial disparities in stroke. After suffering these disparities over a half-century, information is now emerging to allow us to better understand the underpinnings of the disparities and potentially enter a new era of targeted interventions to reduce these disparities.
Abstract 9534: Expression of Heme Oxygenase-1 in Cardiac Stem Cells Enhances the Efficacy of Cell Therapy for Attenuating Left Ventricular Dysfunction and Remodeling After Myocardial Infarction
Authors: Qianhong Li, Yiru Guo, Qinghui Ou, Wen-Jian Wu, Xiaoping Zhu, Li Luo, Jun Li, Roberto Bolli
Journal: Circulation (2012)

Although transplantation of cardiac stem cells (CSCs) improves LV function and structure after myocardial infarction (MI), this salubrious effect is limited by early massive CSC loss due to apoptosis. Heme oxygenase-1 (HO-1) is known to exert potent antiapoptotic and cytoprotective effects. Thus, we hypothesized that expression of HO-1 in CSCs will enhance their survival and reparative ability. To test this hypothesis, lin - /c-kit + CSCs were isolated and expanded from wild-type (WT), HO-1 transgenic (TG) or knockout (KO) mice. HO-1 protein overexpression in HO-1 TG CSCs (confirmed by FACS and immunoblotting) was mild (3-fold greater than WT CSCs). Mice underwent a 60-minute coronary occlusion followed by reperfusion; 48 h later, they received intramyocardial injection of vehicle or WT, HO-1 TG or HO-1 KO CSCs (10 5 CSCs/heart). Sham mice underwent 1-hour open-chest state with no intervention. At 35 days post-MI, both WT and HO-1 TG CSC transplantation resulted in alleviation of LV dysfunction and remodeling compared with vehicle group; however, the magnitude of the beneficial effects of HO-1 TG CSCs was significantly greater than that of WT CSCs. Compared with WT CSCs, transplantation of HO-1 TG CSCs resulted in a greater improvement in global and regional LV function (assessed by two independent methods - echocardiography and conductance catheter) and a greater increase in viable myocardial tissue in the risk region, suggesting increased formation of new cardiomyocytes (Fig). In contrast, transplantation of HO-1 KO CSCs failed to produce any LV structural or functional benefits. These results indicate, for the first time, that even a mild increase in HO-1 promotes CSC competence and that expression of HO-1 is a powerful strategy to enhance the cardiac reparative actions of CSCs in limiting LV dysfunction and remodeling post-MI. The data provide a potential therapeutic approach for promoting myocardial regeneration via modification of CSCs with cytoprotective genes.
Abstract 13139: Prognostic Utility of Contrast-Enhanced Cardiovascular Magnetic Resonance Imaging in Hypertrophic Cardiomyopathy: An International Multicenter Study
Authors: Raymond H Chan, Barry J Maron, Iacopo Olivotto, Gabriele Assenza, John R. Lesser, Tammy Haas, Christiane Gruner, Andrew Crean, Harry Rakowski, James E. Udelson, Ethan Rowin, Benedetta Tomberli, Paolo Spirito, Francesco Formisano, Elena Biagini, Claudio Rapezzi, Carlo Nicola De Cecco, Camillo Autore, Earl Francis Cook, Susie N Hong, C. Michael Gibson, Warren J Manning, Evan Appelbaum, Martin S Maron
Journal: Circulation (2012)

Raymond H Chan, 2012 Finalist and Presenting Author
Abstract 12621: B-Type-Natriuretic Peptide and C-Reactive Protein in the Prediction of Atrial Fibrillation Risk: The CHARGE-AF Consortium
Authors: Moritz F Sinner, Bouwe Krijthe, Thor Aspelund, Katherine Stepas, Michael Pencina, Carlee Moser, Nona Sootodehnia, Joao Fontes, Cecile Janssens, Richard Kronmal, Jared Magnani, Jacqueline Witteman, Alanna Chamberlain, Steven Lubitz, Renate Schnabel, Ramachandran Vasan, Thomas Wang, Sunil Agarwal, David McManus, Patrick Ellinor, Martin Larson, Gregory Burke, Leonore Launer, Albert Hofman, Daniel Levy, John Gottdiener, Stefan Kääb, David Couper, Tamara Harris, Elsayed Soliman, Bruno Stricker, Vilmundur Gudnason, Susan Heckbert, Emelia Benjamin, Alvaro Alonso
Journal: Circulation (2012)

Moritz F Sinner, 2012 Finalist and Presenting Author
Abstract 19780: Mammalian Cardiac Renewal by Preexisting Cardiomyocytes
Authors: Samuel E Senyo, Matthew L. Steinhauser, Christie L Pizzimenti, Vicky K Yang, Mei Wang, Lei Cai, Ting-Di Wu, Jean-Luc Guerquin-Kern, Claude P Lechene, Richard T Lee
Journal: Circulation (2012)

Samuel E Senyo, 2012 Finalist and Presenting Author
Abstract 9968: Reduced Heart Rate Recovery after Exercise is Associated with Mortality After an ICD
Authors: Cynthia M Dougherty, Gayle L Flo, Todd L Goldman, Robert L Burr, Robb L Glenny
Journal: Circulation (2012)

Background and purpose: The period of recovery in heart rate (HRR) after exercise is thought to be mediated by parasympathetic reactivation. Abnormal heart rate recovery (&lt;12 bpm during the 1st minute or &lt; 25 bpm at 5 minutes) after exercise, has been shown to be a powerful predictor of mortality in those with coronary artery disease or heart failure (HF). HRR has not been studied in persons with an ICD. The purpose of this study was to examine the relationship between 1 and 5 minute HRR and 1 year mortality in patients undergoing exercise testing who have an ICD for either primary or secondary prevention of sudden cardiac arrest. Methods: 149 patients who had a previous ICD implant (39% primary indication, 61% secondary indication, mean age 54+12.5 years, 76% male, 3.7+4.3 years since implant, 100% taking beta blockers) entered a clinical trial of exercise after an ICD. At baseline study entry, they completed a cardiopulmonary exercise test using a modified Balke treadmill protocol. HRR was calculated as the difference between peak exercise HR and 1 and 5 minutes into the recovery period using 12 lead EKG recordings. Analysis of variance was used to determine if HRR was significantly related to 1 year mortality after study entry. Results: There were 4 deaths within the 1st year after study entry (2.6%), all had a history of HF. Three deaths were due to HF and 1 was due to cancer. HRR was significantly reduced in those who died at both 1 minute (mean+SD; 7.5+6.2 bpm vs. 18.3+8.1 bpm, F=2.64, p =0.009) and at 5 minutes (19.2+6.0 bpm vs 38.7+13.9 bpm, F=2.76, p =0.006) when compared to those who did not. At baseline, there was statistically higher HRR in secondary prevention (19.4 bpm vs. 16.3 bpm at 1min ( p =0.42) compared to primary prevention (40.7 bpm vs. 33.8 bpm at 5min ( p =0.007). HRR was not related to ICD shocks. Conclusions: Those who have an ICD for primary prevention with a history of HF had lower HRR after exercise testing and higher 1 year mortality than those with a secondary prevention ICD. HRR is a useful marker of autonomic dysregulation and risk for mortality in those with HF who have an ICD.
Abstract 14415: The Sumo Protease Senp2 Regulates Endothelial Dysfunction and Subsequent Atherosclerosis Formation
Authors: Kyungsun Heo, Eugene Chang, Nhat-tu Le, Hannah Cushman, Edward T.H. Yeh, Keigi Fujiwara, Jun-ichi Abe
Journal: Circulation (2012)

Kyungsun Heo, 2012 Finalist and Presenting Author