tbuckley/cabot-search huggingface dataset:
Abstract 418: Perm1 is a Novel Regulator of Mitochondrial Energetics in Cardiomyocytes
Authors: Junco S Warren, Shin-ichi Oka, Maha Abdellatif, Keiko Cawley, Amira Sabry, Christopher Stubben, Brian Dalley, Stavros Drakos, Junichi Sadoshima
Journal: Circulation Research (2018)

Mitochondrial oxidative metabolism and energy transduction pathways are critical for cardiac function. The expression of genes important for mitochondrial energetics is under the control of members of the peroxisome proliferator-activated receptor coactivator 1 (PGC-1) family and the estrogen-related receptor (ERR) subfamily. Perturbations in PGC-1 and/or ERR activities have been associated with impaired mitochondrial function and the development of heart failure. The mechanisms by which PGC-1 and ERR proteins regulate muscle specific transcriptional programs is not fully understood. P GC-1 and E RR-induced r egulator in m uscle 1 (Perm1) was recently identified in skeletal muscle as a muscle-specific key regulator of mitochondrial energetics. Although overexpression of Perm1 enhances oxidative capacity and fatigue resistance in mouse skeletal muscle, the underlying mechanisms remain to be elucidated. Perm1 is highly expressed in mouse and human hearts, and its expression level was reduced in pressure overload-induced heart failure in mice (49.9 ± 12.1% of sham, n=4, p&lt;0.05) and in patients with heart failure (45.5 ± 12.1% of donors, n=5, p&lt;0.05). Moreover, Perm1 is expressed in both the nucleus and the cytoplasm in primary cultured neonatal rat ventricular myocytes (NRVMs) and phenylephrine-induced cellular hypertrophy led to downregulation of Perm1 in both fractions (56.7 ± 1.7% of control). RNAseq followed by bioinformatic analysis revealed that siRNA-mediated Perm1 knockdown (KD) in NRVMs led to global downregulation of ERRα/PGC1α-target genes involved in oxidative phosphorylation, including the electron transport chain and TCA cycle ( Ndufs8; Ndufb8; Cox5a; Cox6a1; Coq2; Cox5a; Cox8a; Coq10b; Sdhb; Sdhd) . Basal respiration and ATP production rates were significantly reduced in Perm1-KD H9c2 rat ventricular myocyte-derived cells (60.4 ± 4.2% and 35.2 ± 8.8% of control cells that were transfected with scrambled-siRNA, both p&lt;0.05). This study demonstrates a novel role of Perm1 in cardiomyocytes that provides an additional layer of mitochondrial energetics regulation, presumably in an ERRα- and PGC1α-mediated manner, and suggests that downregulation of Perm1 may contribute to mitochondrial impairment during heart failure.
DYSREGULATION OF RENIN AND COLLAGEN REMODELING IN ATRIAL FIBRILLATION
Authors: Dimpi Patel, Aleksander Druck, Debra A. Hoppensteadt, Vinod Bansal, Paula Maia, Eugene Brailovsky, Jawed Fareed, Mushabbar A. Syed
Journal: Journal of the American College of Cardiology (2019)
PULMONARY ARTERIAL HYPERTENSION WITH CONCOMITANT LEFT VENTRICULAR DYSFUNCTION: A CHALLENGING CLINICAL SCENARIO
Authors: Luise Holzhauser, Jayant Raikhelkar, Lira Palen, Ann Nguyen, Bow Chung, Gene Kim, Bryan Smith, Nikhil Narang, Imo Ebong, Gabriel Sayer, Nir Uriel
Journal: Journal of the American College of Cardiology (2019)
SIMULTANEOUS LEFT ANTERIOR DESCENDING AND LEFT CIRCUMFLEX ARTERY MYOCARDIAL BRIDGING CAUSING RECURRENT CARDIAC ANGINA IN A YOUNG WOMAN
Authors: Fiorella Llanos-Chea, Cesia Maria, Gallegos Kattan, Raymundo Quintana Quezada, S. Elissa Altin
Journal: Journal of the American College of Cardiology (2019)
Abstract 350: Human Cardiac Fibroblasts Have Angiogenic Inhibitory Phenotypes Through Their Expressing Lypd1 In Vitro
Authors: Katsuhisa Matsuura, Shinako Masuda, Tatsuya Shimizu
Journal: Circulation Research (2018)

Bioengineered cardiac tissues are expected to use for regenerative medicine and tissue model, and tissue vascularization is necessary for fabricating three dimensional thickened cardiac tissues. Consistent with the evidence that fibroblasts are major component cells in heart, they are also imperative for fabricating bioengineered cardiac tissues. Although fibroblasts exist in many tissues and organs, tissue-specific phenotypes of fibroblasts remain unclear, which might make it difficult to fabricate bioengineered tissues close to the biological tissues. As bioengineered tissues provide the micromilieu for mutual communication among multilineage cells, we attempted to identify cardiac fibroblast-specific function against endothelial cells in comparison with dermal tissue-derived fibroblasts and the underlying mechanisms. When human atrial or ventricular cardiac fibroblasts (NHCFa or NHCFv) and dermal tissue-derived fibroblasts (NHDF) were co-cultured with various types of human endothelial cells including HUVEC for 3 days, NHCFa and NHCFv, but not NHDF, significantly inhibited CD31 positive endothelial cell network formation (NHCFa: 1.3±0.3, NHCFv: 2.3±0.1, NHDF: 4.6±0.7, n=3, p&lt;0.05). Then we hypothesized that cardiac fibroblasts express angiogenesis inhibitory factors. We identified genes that were highly expressed in cardiac fibroblasts and encoded extracellular proteins through microarray analysis. After evaluating the effects of candidate genes on endothelial cell network formation by siRNA transfection to cardiac fibroblasts, Ly6/Plaur domain-containing 1 (LYPD1) was identified as the responsible factor. Next we generated recombinant LYPD1 (rLYPD1) and elucidated the effect of rLYPD1 on angiogenesis. Robust endothelial cell network formation in co-culture with NHDF was attenuated with the treatment with rLYPD1 and endothelial tube formation on Matrigel was also remarkably inhibited in the presence of rLYPD1, suggesting that LYPD1 has an angiogenesis inhibitory function. These findings indicate that human cardiac fibroblasts have angiogenesis inhibitory phenotypes through LYPD1 in vitro and inhibition of LYPD1 will be necessary for fabricating vascularized bioengineered cardiac tissues.
TRENDS OF CORONARY ARTERY DISEASE IN KAWASAKI DISEASE IN PATIENTS YOUNGER THAN 18 YEARS OLD FROM THE NATIONWIDE INPATIENT SAMPLE: 2005-2014
Authors: Harshil Shah, Mihir Dave, Achint Patel, Safi Khan, Hee Kong Fong, Reena Motwani, Shobha Mandal, Ashish Sadolikar, Edo Kaluski
Journal: Journal of the American College of Cardiology (2019)
Abstract 227: Inhibition of Histone Deacetylase Catalytic Activity Improves Cardiac and Pulmonary Function in a Feline Model of Heart Failure with Preserved Ejection Fraction
Authors: Markus Wallner, Deborah Eaton, Remus Berretta, Jichuan Wu, Mark Jeong, Ying Lin, Sandy Baker, Mark Oyama, Dirk von Lewinski, Sadia Mohsin, Heiner Post, Timothy McKinsey, Marla Wolfson, Steven R Houser
Journal: Circulation Research (2018)

Rationale: Heart Failure with preserved Ejection Fraction (HFpEF) accounts for about 50% of all heart failure cases but has no effective therapies. Hypothesis: Inhibition of histone deacetylase (HDAC) catalytic activity exerts beneficial effects on the cardiopulmonary system in a feline model of HFpEF. Methods and Results: Male domestic short hair cats (n=21, aged 2mo), underwent either a sham procedure (n=5) or aortic constriction (n=16) using a customized pre-shaped band, resulting in slow progressive pressure overload during growth. 2 months post-banding, banded cats were treated daily with either 10mg/kg suberoylanilide hydroxamic acid ( b+SAHA ) (n=8), a pan-HDAC inhibitor, or vehicle ( b+veh ) (n=8) for 2 months. At 4 months post-banding, b+SAHA cats showed significantly reduced LV wall thickness and LA size (LA/Ao) compared to b+veh cats (Fig). Invasively measured left ventricular end-diastolic pressure (Fig. LVEDP) at 4 months was significantly elevated in b+veh cats compared to b+SAHA and sham cats (Fig). After dobutamine infusion, the increase in dp/dt max was significantly attenuated in b+veh , but not in b+SAHA cats (Fig). In vivo measurements of pulmonary function at 4 months post-banding demonstrated marked improvement in b+SAHA cats, reflected by an increase in lung compliance and a decrease in alveolar-arterial oxygen gradient (A-aDO 2 ) and intrapulmonary shunt (Fig). Efficacy of SAHA in vivo correlated with enhanced ex vivo myofibril relaxation. Conclusion: HDAC inhibition rescues the established HFpEF phenotype by reducing LV hypertrophy, LVEDP, LA size, and enhancing myofibril relaxation, which ultimately results in improved pulmonary function.
ORAL CALCIUM SUPPLEMENTS ASSOCIATE WITH SERIAL CORONARY CALCIFICATION: INSIGHTS FROM INTRAVASCULAR ULTRASOUND
Authors: Najdat Bazarbashi, Rishi Puri, Stephen Nicholls, Julie St. John, Mohamed Gad, Manpreet Kaur, Antonette Karrthik, Yasser Sammour, Keerat Rai Ahuja, E. Murat Tuzcu, Steven Nissen, Samir Kapadia
Journal: Journal of the American College of Cardiology (2019)
TRANSCATHETER VERSUS SURGICAL AORTIC VALVE REPLACEMENT IN ELDERLY PATIENTS: A PROPENSITY SCORE MATCHED ANALYSIS FROM THE NATIONAL READMISSION DATABASE 2011-2015
Authors: Alejandro Lemor, Pedro Villablanca, Gabriel Hernandez, Tiberio Frisoli, Dee Dee Wang, Marvin H. Eng, William W. O'Neill
Journal: Journal of the American College of Cardiology (2019)
RECURRENT SUPRAVENTRICULAR ARRHYTHMIA: WHEN ABLATION IS NOT THE ANSWER – A PERPLEXING CASE OF PHENOCHROMOCYTOMA
Authors: Sarah Gorgis, Mohammed Dabbagh, Sagger Mawri, Gray Akoegbe, Shaheen Alanee, Khaldoon Alaswad, Ali Dabaja, Bobak Rabbani
Journal: Journal of the American College of Cardiology (2019)
Female genital mutilation: barriers to accessing care
Authors: Sharon Dixon, Joy Shacklock, Jonathan Leach
Journal: BMJ (2019)

We thank Creighton and colleagues for their editorial.1 Women affected by female genital mutilation (FGM) describe barriers to accessing medical care in the UK, including fear of judgment by health professionals.2 Recent policy changes, including mandatory reporting and the FGM enhanced dataset, may increase reluctance to see doctors.34

Trust and confidentiality are cornerstones of consultations. Where there are safeguarding concerns, relevant proportionate information should rightly be shared with the relevant agencies. But …
Abstract 549: Interleukin-6 Trans-Signaling in Acute Myocardial Infarction in Male BALB/c Mice
Authors: Nathan A Holland, Robert M Lust, Christopher J Wingard, David A Tulis
Journal: Circulation Research (2018)

Interleukin-6 (IL-6) is a pleiotropic cytokine historically associated with development and/or maintenance of cardiovascular disease (CVD). Despite this long-standing association, the discrete roles of IL-6 on the pathogenesis or severity of CVD and notably acute myocardial infarction (AMI) remain unclear. Dogma contends that IL-6 mediates effects largely through direct interaction with a membrane-bound IL-6 receptor (IL-6R) on leukocytes and hepatocytes. Intriguingly, identification of a soluble receptor for IL-6 (sIL-6R) has invigorated study into a regulatory role of IL-6 trans-signaling (IL-6trans) in CVD pathogenesis. IL-6trans provokes signal transduction in cells lacking the membrane-bound receptor, including notably cardiomyocytes, and ultimately activates STAT3 gene transcription and stabilizes mitochondrial function, thereby promoting cardioprotection. In this study we hypothesized that IL-6trans plays a crucial role in the injury response to AMI by increasing circulating IL-6 and sIL-6R and inducing cardioprotection via STAT3. To test this hypothesis, male BALB/c mice were subjected to acute ischemia (30 min) of the LAD coronary artery (to mimic AMI) with/without reperfusion and with/without inclusion of a pre- or post-ischemic conditioning event in order to determine regulatory involvement of IL-6trans in acute cardioprotection. Following surgery, ischemic regions of left ventricle (LV) and sera were analyzed for IL-6, sIL-6R, and activated (phosphorylated) STAT3. Results show that AMI led to increases in serum IL-6 (p=0.0053) and sIL-6R (p=0.0023) as well as in LV phosphorylated (Tyr705) STAT3 (p=0.0059) compared to naïve LV tissues. Preliminary data from ischemic pre- and post-conditioning regimens were independently associated with increases in IL-6trans demonstrated by trending increases in LV STAT3 phosphorylation (Ser727, Tyr705) compared to naïve controls. These inclusive data on IL-6trans suggest it serves a biologically significant intrinsic role in mediating acute protection following AMI. We anticipate that continued investigation will firmly establish IL-6trans as a unique protective pathway that could be targeted in order to improve morbidity and mortality of AMI patients.
THE IMPACT OF DOOR TO DIURETIC TIME IN ACUTE HEART FAILURE ON HOSPITAL LENGTH OF STAY AND INPATIENT MORTALITY
Authors: Arshad Muhammad Iqbal, Syed Moin Hassan, Salaah Siddiqui, Ateeq Mubarik, Muhammad Zeeshan Ali, Furqan Haq, Abdul Waheed, Salman Muddassir
Journal: Journal of the American College of Cardiology (2019)
DIAGNOSING LEFT VENTRICULAR HYPERTROPHY IN A LARGE, DIVERSE PATIENT POPULATION: ECG VERSUS ECHO
Authors: Maxwell Bressman, Alon Mazori, Eric Shulman, Jay J. Chudow, Ythan Goldberg, Kevin Ferrick, John Fisher, Mario Garcia, Luigi DiBiase, Andrew Krumerman
Journal: Journal of the American College of Cardiology (2019)
Alternative-Donor Hematopoietic Stem Cell Transplantation for Sickle Cell Disease in Pediatric Patients: A Systematic Review and Meta-Analysis
Authors: Eman M. Elsabbagh, Osama Abunar, Ammar Habbal, Mohammad Tanbour, Ahmed Mansour, Mohamed Sarhan, Ahmed Elkaryoni, Sherif M. Badawy
Journal: Blood (2018)
COMPARISON OF LUNG ULTRASOUND AND KILLIP CLASSIFICATION IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION SUBMITTED TO CORONARY ANGIOGRAPHY
Authors: Gustavo Neves De Araujo, Felipe Marques, Fernando Scolari, Anderson Silveira, Guilherme Machado, Julia Custodio, Willian Menegazzo, Sandro C. Goncalves, Tiago L. Leiria, Marco V. Wainstein
Journal: Journal of the American College of Cardiology (2019)
RARE PROTEIN-TRUNCATING VARIANTS IN APOB ASSOCIATE WITH LOWER LOW-DENSITY LIPOPROTEIN CHOLESTEROL, LOWER TRIGLYCERIDES, AND REDUCED RISK OF CORONARY HEART DISEASE
Authors: Akihiro Nomura, Gina Peloso, Amit V. Khera, Mark Chaffin, Hong-Hee Won, Atsushi Nohara, Masa-Aki Kawashiri, Hayato Tada, Frederick Dewey, Sekar Kathiresan
Journal: Journal of the American College of Cardiology (2019)
LONG CHAIN ACYLCARNITINES PREDICT RECOVERY OF LEFT VENTRICULAR FUNCTION AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT FOR SEVERE AORTIC STENOSIS
Authors: Nilay Patel, Qiong Yang, Deborah Furman, Laurie Farrell, Morningstar Jordan, Xu Shi, Robert Gerszten, Brian Lindman, Sammy Elmariah
Journal: Journal of the American College of Cardiology (2019)
Substance misuse in older adults with frailty
Authors: Amanda A B Thompsell, Kapila Sachdev, Jayati Das-Munshi, Tony Rao
Journal: BMJ (2019)

Quinn and colleagues focus on older adults with frailty.1 With over 30% of old age psychiatrists already commissioned to work collaboratively with other colleagues in frailty services,2 we were pleased to see a comprehensive approach taken that …
Abstract 101: Endothelial Arnt Regulates Microvascular Endothelial Barrier Function in Heart Failure Through a Novel Mmp3 Pathway
Authors: Mei Zheng, Maura Knapp, Jorge Andrade, Anna Cheng, Nikola Sladojevic, Konstantin G Birukov, Qiong Zhao, James K. liao, Rongxue (Rosie) Wu
Journal: Circulation Research (2018)

Background: Increased microvascular permeability and cardiac interstitial edema formation are major contributors to progressive myocyte dysfunction during ischemia/reperfusion (IR) injury. Effective clinical therapies for IR injury are lacking, primarily because the mechanisms linking IR to cardiac microvascular permeability and edema are largely unknown. Results from my current studies indicate that vascular permeability is limited by the expression of Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT), a transcription factor that regulates gene expression by homodimerizing or by heterodimerizing with hypoxia-inducible factor (HIF) 1α, HIF2α, or other cofactors. We hypothesize that endothelial ARNT mediates cardiac remodeling following IR. Methods and Results: We have recently generated inducible VE-cadherin-Cre ERT2 endothelial cell (EC)-specific ARNT knockout mice (ecARNT -/- ), which, after ecARNT -/- induction by oral tamoxifen administration, display increased cardiac endothelial permeability with preserved contractile function of the heart. However, after 24 hours of ischemia-reperfusion, ecARNT -/- mice exhibit severe cardiac blood vessel leakage and impaired cardiac function. Following one month of IR, ecARNT -/- mice have a 50% mortality rate, and impaired cardiac function, as determined by EF% and FS%. Only 10% mortality is observed in the control group (ARNTf/f mice treated with tamoxifen). Furthermore, data from microarray analysis show that matrix metalloproteinases (MMPs) are significantly upregulated in ARNT deficient mouse cardiac microvascular endothelial cells (CMVECs), with a particularly significant increase in MMP3. MMP3 can cleave most extracellular matrix constituents and its inhibition attenuates the increase in cell permeability observed in ecARNT -/- CMVECs. Finally, use of an MMP inhibitor in vivo rescues heart failure induced by IR in ecARNT -/- mice. Taken together, these results suggest that ecARNT may mediate heart failure during IR through an MMP3 pathway. Conclusion: Endothelial ARNT is a critical regulator of endothelial function and could potentially serve as a therapeutic target for heart failure in response to IR injury.
ARRHYTHMIA TYPE AND DURATION ON MYOCARDIAL RECOVERY IN PATIENTS WITH ARRHYTHMIA INDUCED CARDIOMYOPATHY: A MULTICENTER STUDY
Authors: Rakesh Gopinathannair, Rahul Dhawan, Brian Olshansky, Andrew Murray, Talha Farid, Sharan Sharma, Dhanunjaya Lakkireddy
Journal: Journal of the American College of Cardiology (2019)
Abstract P137: Rapid Cooling Technology: Ice-slurry on Demand
Authors: Joshua W Lampe, Lance B Becker
Journal: Circulation (2008)

Goal: Animal studies suggest that maximal benefit from hypothermia is achieved when hypothermia is induced during the intra-arrest period before ROSC. Inducing hypothermia before ROSC is a daunting engineering task, as 280 Kcal of energy need to be removed from a 70 kg human to achieve the 4 degrees Celsius of cooling. In a 5 minute timeframe this translates into 3.9 KW of power that needs to be applied to the body. Space and electrical power are significantly limited in the pre hospital scenario. Ice-particulate slurry is a promising phase change coolant that delivers 50% more cooling power per unit volume as ice cold saline. The goal of this project was to create a device that can create a pumpable 50% ice-saline slurry for use as a human coolant on demand from room temperature saline without the requirement of significant electrical power for refrigeration. Methods: Dry ice is used to supply the cooling power for the slurry on demand device. A cooling coil is submerged in a dry ice-alcohol bath. A seco...
DNA-Based Digital PCR for the Quantification of Residual Disease in CML — Sensitivity or Specificity?
Authors: Mary Alikian, Rebecca Ellwood, Olga Tatarinova, Graham David Rose, George Nteliopoulos, Gareth Gerrard, Jamshid S Khorashad, Dragana Milojkovic, Alistair Reid, Letizia Foroni, Richard Clark, Jane Apperley
Journal: Blood (2018)
SITES THAT CONTROL LARGER AREAS DURING ATRIAL FIBRILLATION MAY DETERMINE TERMINATION DURING ABLATION
Authors: Neal K. Bhatia, Samir Hossainy, Albert Rogers, Mahmood Alhusseini, Chad Brodt, Nosheen Moosvi, Tina Baykaner, Paul Wang, Wouter-Jan Rappel, Sanjiv Narayan
Journal: Journal of the American College of Cardiology (2019)
THE IMPACT OF NUCLEAR IMAGING IN PATIENTS WITH ‘POSSIBLE’ INFECTIVE ENDOCARDITIS IN ROUTINE CLINICAL PRACTICE
Authors: Amit Kaura, Margaret Gunning, Amanda Fife, Ranjit Deshpande, Max Baghai, Nicola Mulholland, Gillian Vivian, Philip MacCarthy, Olaf Wendler, Mark Monaghan, Jonathan Byrne, Rafal Dworakowski
Journal: Journal of the American College of Cardiology (2019)
ADVERSE OUTCOMES AFTER ACUTE AORTIC DISSECTION ARE PRECEDED BY CHANGES IN NOVEL AORTIC GROWTH RATIO ON SERIAL IMAGING
Authors: Amit Sharma, Jasmine Curry, Larissa Stanberry, Ross Garberich, Matthew Pavlovec, John Lesser, Jesse Manunga, Domenico Calcaterra, Jessica Titus, Karol Mudy, Kevin Harris
Journal: Journal of the American College of Cardiology (2019)
Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity
Authors: Olof S. Dallner, Jill M. Marinis, Yi-Hsueh. Lu, Kivanc Birsoy, Emory Werner, Gulya Fayzikhodjaeva, Brian D. Dill, Henrik Molina, Arden Moscati, Zoltán Kutalik, Pedro Marques-Vidal, Tuomas O. Kilpeläinen, Niels Grarup, Allan Linneberg, Yinxin Zhang, Roger Vaughan, Ruth J. F. Loos, Mitchell A. Lazar, Jeffrey M. Friedman
Journal: Nature Medicine (2019)
Gene expression signatures of circulating human type 1, 2, and 3 innate lymphoid cells
Authors: Shuo Li, Hideaki Morita, Milena Sokolowska, Ge Tan, Tadech Boonpiyathad, Lennart Opitz, Keisuke Orimo, Stuart K. Archer, Kirstin Jansen, Mimi L.K. Tang, Damian Purcell, Magdalena Plebanski, Cezmi A. Akdis
Journal: Journal of Allergy and Clinical Immunology (2019)
PATIENT PERCEPTIONS AND MANAGEMENT OF CHOLESTEROL AMONG INDIVIDUALS WITH OR WITHOUT DIABETES IN COMMUNITY PRACTICE: RESULTS FROM THE PALM REGISTRY
Authors: Angela Lowenstern, Ann Marie Navar, Shuang Li, Salim Virani, Andrew Koren, Michael Louie, Jennifer Robinson, Veronique Roger, Anne Goldberg, Eric Peterson, Tracy Wang
Journal: Journal of the American College of Cardiology (2019)
THE ASSOCIATION OF P2Y12 INHIBITOR COPAYMENT REDUCTION WITH OUTCOMES AT HOSPITALS WITH AND WITHOUT MEDICATION ASSISTANCE PROGRAMS
Authors: Jacob Appel Doll, Lisa Kaltenbach, Kevin Anstrom, Gregg Fonarow, Christopher Cannon, Timothy Henry, David Cohen, James Eudicone, Eileen Fonseca, Narinder Bhalla, Eric Peterson, Tracy Wang
Journal: Journal of the American College of Cardiology (2019)